Viral Biology

█ BRIAN D. HOYLE/

ABDEL HAKIM NASR

An understanding of the fundamentals of virus structure, genetics, and replication is critical to virologists and other forensic investigators attempting to identify potential biogenic pathogens that may be exploited as agents in biological warfare or by bioterrorists.

Fundamentals of Viral Biology

Viruses are essentially nonliving repositories of nucleic acid that require the presence of a living prokaryotic or eukaryotic cell for the replication of the nucleic acid. There are a number of different viruses that challenge the human immune system and that may produce disease in humans. In general, a virus is a small, infectious agent that consists of a core of genetic material (either deoxyribonucleic acid [DNA] or ribonucleic acid [RNA]) surrounded by a shell of protein. All viruses share the need for a host in order to replicate their deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). The virus commandeers the host's existing molecules for the nucleic acid replication process. There are a number of different viruses. The differences include the disease symptoms they cause, their antigenic composition, type of nucleic acid residing in the virus particle, the way the nucleic acid is arranged, the shape of the virus, and the fate of the replicated DNA. These differences are used to classify the viruses and have often been the basis on which the various types of viruses were named.

Virology, viral classification, types of viruses. Virology is the discipline of microbiology that is concerned with the study of viruses. Viruses can exist in a variety of hosts. Viruses can infect animals (including humans), plants, fungi, birds, aquatic organisms, protozoa, bacteria, and insects. Some viruses are able to infect several of these hosts, while other viruses are exclusive to one host.

The classification of viruses operates by use of the same structure that governs the classification of bacteria. The International Committee on Taxonomy of Viruses established the viral classification scheme in 1966. From the broadest to the narrowest level of classification, the viral scheme is: Order, Family, Subfamily, Genus, Species,

and Strain/type. To use an example, the virus that was responsible for an outbreak of Ebola hemorrhagic fever in a region of Africa called Kikwit is classified as Order Mononegavirales, Family Filoviridae, Genus Filovirus, and Species Ebola virus Zaire.

In the viral classification scheme, all families end in the suffix viridae, for example Picornaviridae. Genera have the suffix virus. For example, in the family Picornaviridae there are five genera: enterovirus, cardiovirus, rhinovirus, apthovirus, and hepatovirus. The names of the genera typically derive from the preferred location of the virus in the body (for those viral genera that infect humans). As examples, rhinovirus is localized in the nasal and throat passages, and hepatovirus is localized in the liver. Finally, within each genera there can be several species.

There are a number of criteria by which members of one grouping of viruses can be distinguished from those in another group. For the purposes of classification, however, three criteria are paramount. These criteria are the host organism or organisms that the virus utilizes, the shape of the virus particle, and the type and arrangement of the viral nucleic acid.

An important means of classifying viruses concerns the type and arrangement of nucleic acid in the virus particle. Some viruses have two strands of DNA, analogous to the double helix of DNA that is present in prokaryotes such as bacteria and in eukaryotic cells. Some viruses, such as the Adenoviruses, replicate in the nucleus of the host using the replication machinery of the host. Other viruses, such as the Poxviruses, do not integrate in the host genome, but replicate in the cytoplasm of the host. Another example of a double-stranded DNA virus are the Herpesviruses.

Other viruses only have a single strand of DNA. An example is the Parvoviruses. Viruses such as the Parvoviruses replicate their DNA in the host's nucleus. The replication involves the formation of what is termed a negative-sense strand of DNA, which is a blueprint for the subsequent formation of the RNA and DNA used to manufacture the new virus particles.

The genome of other viruses, such as Reoviruses and Birnaviruses, is comprised of double-stranded RNA. Portions of the RNA function independently in the production of a number of so-called messenger RNAs, each of which produces a protein that is used in the production of new viruses.

Still other viruses contain a single strand of RNA. In some of the single-stranded RNA viruses, such as Picornaviruses, Togaviruses, and the Hepatitis A virus, the RNA is read in a direction that is termed "+ sense." The sense strand is used to make the protein products that form the new virus particles. Other single-stranded RNA viruses contain what is termed a negative-sense strand. Examples are the Orthomyxoviruses and the Rhabdoviruses. The negative strand is the blueprint for the formation of the messenger RNAs that are required for production of the various viral proteins.

Still another group of viruses have + sense RNA that is used to make a DNA intermediate. The intermediate is used to manufacture the RNA that is eventually packaged into the new virus particles. The main example is the Retroviruses (e.g. the Human Immunodeficiency viruses). Finally, a group of viruses consist of double-stranded DNA that is used to produce a RNA intermediate. An example is the Hepadnaviruses.

An aspect of virology is the identification of viruses. Often, the diagnosis of a viral illness relies, at least initially, on the visual detection of the virus. For this analysis, samples are prepared for electron microscopy using a technique called negative staining, which highlights surface detail of the virus particles. For this analysis, the shape of the virus is an important feature.

A particular virus will have a particular shape. For example, viruses that specifically infect bacteria, the socalled bacteriophages, look similar to the Apollo lunar lander (LEM spacecraft). A head region containing the nucleic acid is supported on a number of spider-like legs. Upon encountering a suitable bacterial surface, the virus acts like a syringe, to introduce the nucleic acid into the cytoplasm of the bacterium.

Other viruses have different shapes. These include spheres, ovals, worm-like forms, and even irregular (pleomorphic) arrangements. Some viruses, such as the influenza virus, have projections sticking out from the surface of the virus. These are crucial to the infectious process.

As new species of eukaryotic and prokaryotic organisms are discovered, no doubt the list of viral species will continue to grow.

Viral genetics. Viral genetics, the study of the genetic mechanisms that operate during the life cycle of viruses, utilizes biophysical, biological, and genetic analyses to study the viral genome and its variation.

The virus genome consists of only one type of nucleic acid, which could be a single or double stranded DNA or RNA. Single stranded RNA viruses could contain positive-sense (+RNA), which serves directly as mRNA or negative-sense RNA (−RNA) that must use an RNA polymerase to synthesize a complementary positive strand to serve as mRNA. Viruses are obligate parasites that are completely dependant on the host cell for the replication and transcription of their genomes as well as the translation of the mRNA transcripts into proteins. Viral proteins usually have a structural function, making up a shell around the genome, but may contain some enzymes that are necessary for the virus replication and life cycle in the host cell. Both bacterial virus (bacteriophages) and animal viruses play an important role as tools in molecular and cellular biology research.

Viruses are classified in two families depending on whether they have RNA or DNA genomes and whether these genomes are double or single stranded. Further subdivision into types takes into account whether the genome consists of a single RNA molecule or many molecules as in the case of segmented viruses. Four types of bacteriophages are widely used in biochemical and genetic research. These are the T phages, the temperate phages typified by bacteriophage lambda, the small DNA phages like M13, and the RNA phages. Animal viruses are subdivided in many classes and types. Class I viruses contain a single molecule of double stranded DNA and are exemplified by adenovirus, simian virus 40 (SV 40), herpes viruses and human papillomaviruses. Class II viruses are also called parvoviruses and are made of single stranded DNA that is copied in to double stranded DNA before transcription in the host cell. Class III viruses are double stranded RNA viruses that have segmented genomes which means that they contain 10–12 separate double stranded RNA molecules. The negative strands serve as template for mRNA synthesis. Class IV viruses, typified by poliovirus, have single plus strand genomic RNA that serves as the mRNA. Class V viruses contain a single negative strand RNA which serves as the template for the production of mRNA by specific virus enzymes. Class VI viruses are also known as retroviruses and contain double stranded RNA genome. These viruses have an enzyme called reverse transcriptase that can both copy minus strand DNA from genomic RNA catalyze the synthesis of a complementary plus DNA strand. The resulting double stranded DNA is integrated in the host chromosome and is transcribed by the host own machinery. The resulting transcripts are either used to synthesize proteins or produce new viral particles. These new viruses are released by budding, usually without killing the host cell. Both HIV and HTLV viruses belong to this class of viruses.

Virus genetics is studied by either investigating genome mutations or exchange of genetic material during the life cycle of the virus. The frequency and types of genetic variations in the virus are influenced by the nature of the viral genome and its structure. Especially important are the type of the nucleic acid that influence the potential for the viral genome to integrate in the host, and the segmentation that influence exchange of genetic information through assortment and recombination.

Mutations in the virus genome could either occur spontaneously or be induced by physical and chemical means. Spontaneous mutations that arise naturally as a result of viral replication are either due to a defect in the genome replication machinery or to the incorporation of an analogous base instead of the normal one. Induced virus mutants are obtained by either using chemical mutants like nitrous oxide that acts directly on bases and modify them or by incorporating already modified bases in the virus genome by adding these bases as substrates during virus replication. Physical agents such as ultraviolet light and x rays can also be used in inducing mutations. Genotypically, the induced mutations are usually point mutations, deletions, and rarely insertions. The phenotype of the induced mutants is usually varied. Some mutants are conditional lethal mutants. These could differ from the wild type virus by being sensitive to high or low temperature. A low temperature mutant would for example grow at 31°C but not at 38°, while the wild type will grow at both temperatures. A mutant could also be obtained that grows better at elevated temperatures than the wild type virus. These mutants are called hot mutants and may be more dangerous for the host because fever, which usually slows the growth of wild type virus, is ineffective in controlling them. Other mutants that are usually generated are those that show drug resistance, enzyme deficiency or an altered pathogenicity or host range. Some of these mutants cause milder symptoms compared to the parental virulent virus and usually have potential in vaccine development as exemplified by some types of influenza vaccines.

Besides mutation, new genetic variants of viruses also arise through exchange of genetic material by recombination and reassortment. Classical recombination involves breaking of covalent bonds within the virus nucleic acid and exchange of some DNA segments followed by rejoining of the DNA break. This type of recombination is almost exclusively reserved to DNA viruses and retroviruses. RNA viruses that do not have a DNA phase rarely use this mechanism. Recombination usually enables a virus to pick up genetic material from similar viruses and even from unrelated viruses and the eukaryotic host cells. Exchange of genetic material with the host is especially common with retroviruses. Reassortment is a non-classical kind of recombination that occurs if two variants of a segmented virus infect the same cell. The resulting progeny virions may get some segments from one parent and some from the other. All known segmented virus that infect humans are RNA viruses. The process of reassortment is very efficient in the exchange of genetic material and is used in the generation of viral vaccines especially in the case of influenza live vaccines. The ability of viruses to exchange genetic information through recombination is the basis for virus-based vectors in recombinant DNA technology and hold great promises in the development of gene therapy. Viruses are attractive as vectors in gene therapy because they can be targeted to specific tissues in the organs that the virus usually infect and because viruses do not need special chemical reagents called transfectants that are used to target a plasmid vector to the genome of the host.

Genetic variants generated through mutations, recombination or reassortment could interact with each other if they infected the same host cell and prevent the appearance of any phenotype. This phenomenon, where each mutant provide the missing function of the other while both are still genotypically mutant, is known as complementation. It is used as an efficient tool to determine if mutations are in a unique or in different genes and to reveal the minimum number of genes affecting a function. Temperature sensitive mutants that have the same mutation in the same gene will for example not be able to complement each other. It is important to distinguish complementation from multiplicity reactivation where a higher dose of inactivated mutants will be reactivated and infect a cell because these inactivated viruses cooperate in a poorly understood process. This reactivation probably involves both a complementation step that allows defective viruses to replicate and a recombination step resulting in new genotypes and sometimes regeneration of the wild type. The viruses that need complementation to achieve an infectious cycle are usually referred to as defective mutants and the complementing virus is the helper virus. In some cases, the defective virus may interfere with and reduce the infectivity of the helper virus by competing with it for some factors that are involved in the viral life cycle. These defective viruses called "defective interfering" are sometimes involved in modulating natural infections. Different wild type viruses that infect the same cell may exchange coat components without any exchange of genetic material. This phenomenon, known as phenotypic mixing is usually restricted to related viruses and may change both the morphology of the packaged virus and the tropism or tissue specificity of these infectious agents.

Virus replication. Viral replication refers to the means by which virus particles make new copies of themselves. Although precise mechanisms vary, viruses cause disease by infecting a host cell and commandeering the host cell's synthetic capabilities to produce more viruses. The newly made viruses then leave the host cell, sometimes killing it in the process, and proceed to infect other cells within the host.

Viruses cannot replicate by themselves. They require the participation of the replication equipment of the host cell that they infect in order to replicate. The molecular means by which this replication takes place varies, depending upon the type of virus.

Viral replication can be divided up into three phases: initiation, replication, and release.

The initiation phase occurs when the virus particle attaches to the surface of the host cell, penetrates into the cell and undergoes a process known as uncoating, where the viral genetic material is released from the virus into the host cell's cytoplasm. The attachment typically involves the recognition of some host surface molecules by a corresponding molecule on the surface of the virus. These two molecules can associate tightly with one another, binding the virus particle to the surface. A well-studied example is the haemagglutinin receptor of the influenzae virus. The receptors of many other viruses have also been characterized.

A virus particle may have more than one receptor molecule, to permit the recognition of different host molecules, or of different regions of a single host molecule. The molecules on the host surface that are recognized tend to be those that are known as glycoproteins. For example, the human immunodeficiency virus recognizes a host glycoprotein called CD4. Cells lacking CD4 cannot, for example, bind the HIV particle.

Penetration of the bound virus into the host interior requires energy. Accordingly, penetration is an active step, not a passive process. The penetration process can occur by several means. For some viruses, the entire particle is engulfed by a membrane-enclosed bag produced by the host (a vesicle) and is drawn into the cell. This process is called endocytosis. Polio virus and orthomyxovirus enters a cell via this route. A second method of penetration involves the fusion of the viral membrane with the host membrane. Then the viral contents are directly released into the host. HIV, paramyxoviruses, and herpes viruses use this route. Finally, but more rarely, a virus particle can be transported across the host membrane. For example, poliovirus can cause the formation of a pore through the host membrane. The viral DNA is then released into the pore and passes across to the inside of the host cell.

Once inside the host, the viruses that have entered via endocytosis or transport across the host membrane need to release their genetic material. With poxvirus, viral proteins made after the entry of the virus into the host are needed for uncoating. Other viruses, such as adenoviruses, herpesviruses, and papovaviruses associate with the host membrane that surrounds the nucleus prior to uncoating. They are guided to the nuclear membrane by the presence of so-called nuclear localization signals, which are highly charged viral proteins. The viral genetic material then enters the nucleus via pores in the membrane. The precise molecular details of this process remains unclear for many viruses.

For animal viruses, the uncoating phase is also referred to as the eclipse phase. No infectious virus particles can be detected during that 10 to 12 hour period of time.

In the replication, or synthetic, phase the viral genetic material is converted to deoxyribonucleic acid (DNA), if the material originally present in the viral particle is ribonucleic acid (RNA). This so-called reverse transcription process needs to occur in retroviruses, such as HIV. The DNA is imported into the host nucleus where the production of new DNA, RNA, and protein can occur. The replication phase varies greatly from virus type to virus type. However, in general, proteins are manufactured to ensure that the cell's replication machinery is harnessed to permit replication of the viral genetic material, to ensure that this replication of the genetic material does indeed occur, and to ensure that this newly made material is properly packaged into new virus particles.

Replication of the viral material can be a complicated process, with different stretches of the genetic material being transcribed simultaneously, with some of these gene products required for the transcription of other viral genes. Also replication can occur along a straight stretch of DNA, or when the DNA is circular (the so-called "rolling circle" form). RNA-containing viruses must also undergo a reverse transcription from DNA to RNA prior to packaging of the genetic material into the new virus particles.

In the final stage, the viral particles are assembled and exit the host cell. The assembly process can involve helper proteins, made by the virus or the host. These are also called chaperones. Other viruses, such as tobacco mosaic virus, do not need these helper chaperones, as the proteins that form the building blocks of the new particles spontaneously self-assemble. In most cases, the assembly of viruses is symmetrical; that is, the structure is the same throughout the viral particle. For example, in the tobacco mosaic virus, the proteins constituents associate with each other at a slight angle, producing a symmetrical helix. Addition of more particles causes the helix to coil "upward" forming a particle. An exception to the symmetrical assembly is the bacteriophage. These viruses have a head region that is supported by legs that are very different in structure. Bacteriophage assembly is very highly coordinated, involving the separate manufacture of the component parts and the direct fitting together of the components in a sequential fashion.

Release of viruses can occur by a process called budding. A membrane "bleb" containing the virus particle is formed at the surface of the cell and is pinched off. For herpes virus this is in fact how the viral membrane is acquired. In other words, the viral membrane is a host-derived membrane. Other viruses, such as bacteriophage, may burst the host cell, spewing out the many progeny virus particles. But many viruses do not adopt such a host destructive process, as it limits the time of an infection due to destruction of the host cells needed for future replication.

█ FURTHER READING:

BOOKS:

Doerfler, Walter, and Petra Bohm, eds. Virus Strategies: Molecular Biology and Pathenogenesis. New York: VCH, 1993.

Flint, S. J., et al. Principles of Virology: Molecular Biology, Pathogenesis, and Control. Washington: American Society for Microbiology, 1999.

Kurstak, Edouard, ed. Control of Virus Diseases. New York: Marcel Dekker, 1993.

Richman, D. D., and R. J. Whitley. Clinical Virology. 2nd ed. Washington: American Society for Microbiology, 2002.

Thomas, D. Brian. Viruses and the Cellular Immune Response. New York: Marcel Dekker, 1993.

PERIODICALS:

Peters, C. J., and J. W. LeDuc. "An Introduction to Ebola: The Virus and the Disease." The Journal of Infectious Diseases no. 179 (Supplement 1, February 1999): ix–xvi.

ELECTRONIC:

Biology Pages. "Viruses." 2002. <http://www.ultranet.com/~jkimball/BiologyPages/V/Viruses.htm>l> (April 12, 2003).

SEE ALSO

Bacterial Biology
Biological and Toxin Weapons Convention
Biological Warfare
Biological Weapons, Genetic Identification
Bioshield Project
Bioterrorism
Bioterrorism, Protective Measures

Viral Biology

Virology is the discipline of microbiology that is concerned with the study of viruses. Knowledge of the basics of viral biology, viral reproduction (viral replication), and the ability to identify potential virus-related pathologies are increasingly important skills for some forensic scientists. There are a number of different viruses that challenge the human immune system and that may produce disease in humans. Although virologists are the scientists most directly concerned with viral biology, with the rise of terrorism and global health issues such as the evolving H5N1 influenza (commonly called bird flu), forensic scientists now find that their work overlaps interests in epidemiology and/or national security.

Viruses are essentially nonliving repositories of nucleic acid that require the presence of a living prokaryotic cell (where DNA is present in the cytoplasm) or eukaryotic cell (where DNA is present within the nucleus) for the replication of the nucleic acid. They can exist in a variety of hosts. Viruses can infect animals (including humans), plants, fungi, birds, aquatic organisms, protozoa, bacteria, and insects. Some viruses are able to infect several of these hosts, while other viruses are exclusive to one host.

Viral replication refers to the means by which virus particles make new copies of themselves. All viruses share the need for a host in order to replicate their deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). The virus commandeers the host's existing molecules for the nucleic acid replication process. There are a number of different viruses. The differences include the disease symptoms they cause, their antigenic composition, type of nucleic acid residing in the virus particle, the way the nucleic acid is arranged, the shape of the virus, and the fate of the replicated DNA. These differences are used to classify the viruses and have often been the basis on which the various types of viruses were named.

The classification of viruses operates by use of the same structure that governs the classification of bacteria . The International Committee on Taxonomy of Viruses established the viral classification scheme in 1966. From the broadest to the narrowest level of classification, the viral scheme is: Order, Family, Subfamily, Genus, Species, and Strain/type. To use an example, the virus that was responsible for an outbreak of Ebola hemorrhagic fever in a region of Africa called Kikwit is classified as Order Mononegavirales, Family Filoviridae, Genus Filovirus, and Species Ebola Zaire.

In the viral classification scheme, all families end in the suffix viridae, for example Picornaviridae. Genera have the suffix virus. In the family Picornaviridae there are five genera: enterovirus, cardiovirus, rhinovirus, apthovirus, and hepatovirus. The names of the genera typically derive from the preferred location of the virus in the body (for those viral genera that infect humans). As examples, rhinovirus is localized in the nasal and throat passages, and hepatovirus is localized in the liver. Finally, within each genera there can be several species.

As noted above, there are a number of criteria by which members of one grouping of viruses can be distinguished from those in another group. For the purposes of classification, however, three criteria are paramount. These criteria are the host organism or organisms that the virus utilizes, the shape of the virus particle, and the type and arrangement of the viral nucleic acid.

An important means of classifying viruses concerns the type and arrangement of nucleic acid in the virus particle. Some viruses have two strands of DNA, analogous to the double helix of DNA that is present in prokaryotes such as bacteria and in eukaryotic cells. Some viruses, such as the Adenoviruses, replicate in the nucleus of the host using the replication machinery of the host. Other viruses, such as the Poxviruses, do not integrate in the host genome, but replicate in the cytoplasm of the host. Another example of a double-stranded DNA virus is the Herpesviruses. Other viruses only have a single strand of DNA such as the Parvoviruses, which can replicate their DNA in the host's nucleus. The replication involves the formation of what is termed as a negative-sense strand of DNA, a blueprint for the subsequent formation of the RNA and DNA used to manufacture the new virus particles.

The genome of other viruses, such as Reoviruses and Birnaviruses, is comprised of double-stranded RNA. Portions of the RNA function independently in the production of a number of so-called messenger RNAs, each of which produces a protein that is used in the production of new viruses. Other viruses contain a single strand of RNA. In some of the single-stranded RNA viruses, such as Picornaviruses, Togaviruses, and the Hepatitis A virus, the RNA is read in a direction that is termed "+ sense." The sense strand is used to make the protein products that form the new virus particles. Other single-stranded RNA viruses contain what is termed a negative-sense strand. Examples are the Orthomyxoviruses and the Rhabdoviruses. The negative strand is the blueprint for the formation of the messenger RNAs that are required for production of the various viral proteins.

Still another group of viruses have + sense RNA that contains the code for a DNA intermediate. The intermediate is used to manufacture the RNA that is eventually packaged into the new virus particles. The main example is the Retroviruses (the Human Immunodeficiency Viruses belong here). Finally, a group of viruses consist of double-stranded DNA that contains the code for an RNA intermediate. An example is the Hepadnaviruses.

One aspect of virology is the identification of viruses. Often, the diagnosis of a viral illness relies, at least initially, on the visual detection of the virus. Samples are prepared for electron microscopy using a technique called negative staining, which highlights surface detail of the virus particles. For this analysis, the shape of the virus is an important feature.

Any particular virus will have an attached shape. For example, viruses that specifically infect bacteria, the so-called bacteriophages, look similar to the Apollo lunar-landing spacecraft. A head region containing the nucleic acid is supported on a number of spider-like legs. Upon encountering a suitable bacterial surface, the virus acts like a syringe, to introduce the nucleic acid into the cytoplasm of the bacterium.

Other viruses have different shapes. These include spheres, ovals, worm-like forms, and even pleomorphic (irregular) arrangements. Some viruses, such as the influenza virus, have projections sticking out from the surface of the virus. These are crucial to the infectious process. As new species of eukaryotic and prokaryotic organisms are discovered, no doubt the list of viral species will continue to grow.

Viruses cannot replicate by themselves. They require the participation of the replication equipment of the host cell that they infect in order to replicate. The molecular means by which this replication takes place varies, depending upon the type of virus. Viral replication can be divided into three phases: initiation, replication, and release.

The initiation phase occurs when the virus particle attaches to the surface of the host cell, penetrates into the cell, and undergoes a process known as uncoating, where the viral genetic material is released from the virus into the host cell's cytoplasm. The attachment typically involves the recognition of some host surface molecules by a corresponding molecule on the surface of the virus. These two molecules can associate tightly with one another, binding the virus particle to the surface. A well-studied example is the haemagglutinin receptor of the influenzae virus. The receptors of many other viruses have also been characterized.

A virus particle may have more than one receptor molecule, to permit the recognition of different host molecules, or of different regions of a single host molecule. The molecules on the host surface that are recognized tend to be those that are known as glycoproteins. For example, the human immunodeficiency virus recognizes a host glycoprotein called CD4. Cells lacking CD4 cannot, for example, bind the HIV particle.

In the replication, or synthetic, phase the viral genetic material is converted to deoxyribonucleic acid (DNA) if the material originally present in the viral particle is ribonucleic acid (RNA). This so-called reverse transcription process needs to occur in retroviruses, such as HIV. The DNA is imported into the host nucleus where the production of new DNA, RNA, and protein can occur. The replication phase varies greatly from virus type to virus type. However, in general, proteins are manufactured to ensure that: the cell's replication machinery is harnessed to permit replication of the viral genetic material; the replication of the genetic material does indeed occur; and the newly made material is properly packaged into new virus particles.

Replication of the viral material can be a complicated process, with different stretches of the genetic material being transcribed simultaneously with some of these gene products required for the transcription of other viral genes. Also, replication can occur along a straight stretch of DNA, or when the DNA is circular (the so-called "rolling circle" form). RNA-containing viruses must also undergo a reverse transcription from DNA to RNA prior to packaging of the genetic material into the new virus particles.

In the final stage, the viral particles are assembled and exit the host cell. The assembly process can involve helper proteins, made by the virus or the host.

Release of viruses can occur by a process called budding. A membrane "bleb" containing the virus particle is formed at the surface of the cell and is pinched off. For herpes virus this is in fact how the viral membrane is acquired. In other words, the viral membrane is a host-derived membrane. Other viruses, such as bacteriophage, may burst the host cell, spewing out the many progeny virus particles. But many viruses do not adopt such a host destructive process, as it limits the time of an infection due to destruction of the host cells needed for future replication.

Although precise mechanisms vary, viruses cause disease by infecting a host cell and commandeering the host cell's synthetic capabilities to produce more viruses. The newly made viruses then leave the host cell, sometimes killing it in the process, and proceed to infect other cells within the host. Because viruses invade cells, drug therapies have not yet been designed to kill viruses, although some have been developed to inhibit their growth. The human immune system is the main defense against a viral disease.

Bacterial viruses, called bacteriophages, infect a variety of bacteria, such as Escherichia coli, a bacteria commonly found in the human digestive tract. Animal viruses cause a variety of fatal diseases. Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV); hepatitis and rabies are viral diseases; and hemorrhagic fevers, which are characterized by severe internal bleeding, are caused by filoviruses. Other animal viruses cause some of the most common human diseases. Often, these diseases strike in childhood. Measles, mumps, and chickenpox are viral diseases. The common cold and influenza are also caused by viruses. Finally, some viruses can cause cancer and tumors. One such virus, human T-cell leukemia virus (HTLV), was only recently discovered and its role in the development of a particular kind of leukemia is still being clarified.

Edward Jenner (1749–1823) is credited with developing the first successful vaccine against a viral disease, with his vaccine for smallpox . A vaccine works by eliciting an immune response. During this immune response, specific immune cells, called memory cells, are produced that remain in the body long after the foreign microbe present in a vaccine has been destroyed. When the body again encounters the same kind of microbe, the memory cells quickly destroy the microbe. Vaccines contain either a live, altered version of a virus or bacteria, or they contain only parts of a virus or bacteria, enough to elicit an immune response.

In 1797, Jenner developed his smallpox vaccine by taking infected material from a cowpox lesion on the hand of a milkmaid. Cowpox was a common disease of the era, transmitted through contact with an infected cow. Unlike smallpox, however, cowpox is a much milder disease. Using the cowpox pus, he inoculated an eight-year-old boy. Jenner continued his vaccination efforts through his lifetime. Until 1976, children were routinely vaccinated with the smallpox vaccine, called vaccinia. Reactions to the introduction of the vaccine ranged from a mild fever to severe complications, including (although very rarely) death. In 1977, when the last naturally occurring case of smallpox appeared and the global eradication of smallpox was complete, vaccinia vaccinations for children were discontinued, although vaccinia continues to be used as a carrier for recombinant DNA techniques. In these techniques, foreign DNA is inserted in cells. Efforts to produce a vaccine for HIV, for instance, have used vaccinia as the vehicle that carries specific parts of HIV.

see also Bacterial biology; Careers in forensic science; Ebola virus; Pathogens; Vaccines; Variola virus.

VIRUSES

Viruses are computer programs, usually malicious but occasionally unintentional, that spread through networks replicating themselves on shared programs and corrupting the computers in their path. While viruses have existed for years, they have taken on a new prominence and danger in the Internet Age, when they can spread much faster and compromise more—and more important—systems. A vast industry arose to combat viruses, but it was largely engaged in an arms race in the early 2000s, as viruses continued to proliferate and mutate, growing more powerful and damaging.

Since computers and networking have become such a central component of economic and social activity, virus attacks, even relatively minor ones, have the potential to severely disrupt daily life. Out of that growing recognition, governments, corporations, and organizations, were coordinating efforts to prepare for and respond to computer viruses.

In a 2001 report titled Virus Prevalence Survey, the Reston, Virginia-based Internet security assurance firm ICSA.net reported that the number of companies that experienced major virus-related disasters increased more than 20 percent in 2000, while 40 percent of companies reported data losses from virus attacks. The report also noted that a typical company spent between $100,000 and $1 million on virus disasters and protection each year, and that figure was rising.

ICSA reported that the prevalence of virus attacks has increased from about 10 per 10,000 computers in 1996 to 91 per 10,000 in 2000, and analysts warned that the proportion would rise in the early 2000s. To make matters worse, each generation of viruses grows more sophisticated. In the early 2000s, virus hunters were challenged by new breeds of self-replicating and mutating viruses that change shape as they spread so as to avoid detection. Virus programmers increasingly incorporate encryption schemes into the programs so as to shield the source code, and metamorphic viruses include a mutation engine in their algorithms that enable them to alter slightly at each replication.

HOW VIRUSES WORK

To perform its function, a virus need only be able to replicate itself. Once a virus infects a computer—by e-mail, disk, or some other method—the program to which the virus is attached only has to be executed to trigger the virus into action. On top of mere replication, viruses may include a malicious payload, a mark that invites the user to perform an operation, such as opening an e-mail attachment. For example, the tag "I LOVE YOU" in the worm virus of the same name in 2000 constituted that virus's payload.

Viruses work in a variety of ways to disrupt a system, but the most common method was to simply overburden it by repeating the same messages over and over via rapid self-replications, eventually crashing the system. In addition, a computer virus may not take effect immediately. It can sit undetected in computer systems for months waiting for the right operation to trigger it into action. By that time, it may be quite difficult to retrace the steps of how a virus was lodged in a system to begin with.

TYPES OF VIRUSES

File infectors target data and executable files on a system's hard drive, and spread primarily by attaching themselves to such files as they spread through a system that uses shared programs. Since executable files are far less likely to be shared over diskettes or e-mail than are data files, according to Security Management, file infectors don't tend to be as successful at spreading outside of local networks.

Boot-sector infectors (BSIs) attack the master boot record the computer taps to start up. BSIs are among the most difficult virus programs to write, according to Security Management, and their claim on the virus population was declining since they don't tend to proliferate over networks and are spread primarily by diskette rather than by e-mail. Modern networking technology, then, was phasing out BSIs, although by the early 2000s they still constituted a significant threat.

Macro viruses attach themselves to those programs that alleviate computer users from performing repetitive tasks, and have grown more prominent in an environment of sophisticated personal computers with many automated macros. Macros are also frequently attached to data files, thus speeding the spread of macro viruses.

Worms were a particular subset of viruses that distinguish themselves by replicating across networks without ever directly attaching themselves to a host program, although the most widely publicized worm viruses were spread as e-mail attachments. Generally, worms invade an individual's computer through e-mail, and then use that individual's e-mail address list to send themselves to others. Worms are characterized by the speed with which they spread through systems; several major worms, such as Melissa and LoveLetter, spread globally before anti-virus players had even detected the problem, much less devised a disinfection program.

Trojan horses, as the Homeric name implies, distinguish themselves by deceit. They appear to the user as benign or beneficial, but instead—or in addition—perform unwanted and potentially destructive functions. Some Trojan horses directly attack files or programs, while others compromise security measures, most commonly by stealing passwords. Still other Trojan horses do no damage at all, but pretend to. These are joke or hoax programs that deceive the user into believing an infection has occurred.

FENDING OFF VIRUSES

By the early 2000s, virus attacks, or threats thereof, were so frequent that businesses were hard pressed to be prepared in advance for all potential attacks. Since predicting when or how a virus would occur was nearly impossible, most businesses, governments, and organizations devoted their efforts to detection, containment, and disinfection programs.

Scores of antivirus vendors specialize in software designed to detect incoming viruses and deflect them from their targets. Since viruses are constantly evolving, so are the programs designed to thwart them, and many organizations, particularly IT-intensive businesses, must make frequent online trips to those vendors' sites to acquire the latest virus patches and other updates. Once these fortifications are acquired, IT security personnel must allocate all the updates to their proper locations, which can be a tedious and time-consuming process.

Antivirus programs typically work by scanning all incoming information for known viruses by seeking out virus "signatures," or tell-tale signs of previously detected viruses. Such signatures generally include known programming patterns and codes, as well as more overt characteristics such as file names or types of e-mail attachments. But by its nature, this method forces antivirus vendors to continually play catch-up with viruses, and vendors are judged not only by the success of their products in fortifying systems against viruses, but also by how proactive they are in anticipating new virus strains. At any rate, IT security staffs are compelled to continually download the latest signature updates. With dozens of vendors issuing such updates, the task of regularly allocating the fortifications to their proper locations was increasingly costly, provoking many analysts to begin calling for more effective and user-friendly methods.

To make such tasks more manageable, antivirus vendors increasingly designed products for the server level, rather than the computer level. Not only were server-level virus screens easier to implement, they were increasingly practical as viruses were spread over server-based vehicles like e-mail. In addition, this provided multiple layers of security so that if an antivirus program failed to stop a virus at one level, it might still be thwarted at another level.

The emerging generation of antivirus programs may render obsolete the daunting task of updating signatures at the desktop level. Increasingly sophisticated programs were aimed at identifying and thwarting viruses based not on comparing their characteristics to lists of previous viruses, but by seeking out malicious behavior. This would be a huge step in the virus-antivirus arms race, allowing antivirus vendors to stop playing catch-up with virus programmers.

One obstacle to virus detection and eradication, according to some analysts, was the propensity of firms to keep internal virus damage quiet so as to avoid compromise of their stock prices or to otherwise try to circumvent financial or competitive disadvantage. While such practices can save a business from short-term headaches, it could also prove an obstacle to broader virus response techniques, since information sharing is so essential in order to get a handle on viruses.

FURTHER READING:

Greiner, Lynn. "IT's Battleground: The Quest for Virus Protection." Computing Canada, August 4, 2000.

Harley, David. "Living with Viruses." Security Management, August 2000.

Messmer, Ellen. "Experts Predict More Mutating Viruses." Network World, October 30, 2000.

Montana, John C. "Viruses and the Law: Why the Law is Ineffective." Information Management Journal, October 2000.

Nevin, Tom. "Computer Virus—Know the Enemy." African Business, April 2001.

Rash, Wayne. "What To Do When The Usual Security Steps Aren't Enough." InternetWeek, August 20, 2001.

Scheier, Robert L. "Managing the Virus Threat." Computer-world, May 7, 2001.

Trembly, Ara C. "The 10 Most Unwanted: 2001's Most Popular Viruses." National Underwriter, August 20, 2001.

"Viruses Rise, Criminals Walk, Public Confidence Falls." Security, February 2001.

SEE ALSO: Computer Crime; Denial of Service Attack; National Information Infrastructure Protection Act of 1996; National Infrastructure Protection Center; Computer Security; Worms

Viral genetics

Viral genetics, the study of the genetic mechanisms that operate during the life cycle of viruses , utilizes biophysical, biological, and genetic analyses to study the viral genome and its variation. The virus genome consists of only one type of nucleic acid, which could be a single or double stranded DNA or RNA . Single stranded RNA viruses could contain positive-sense (+RNA), which serves directly as mRNA or negative-sense RNA (–RNA) that must use an RNA polymerase to synthesize a complementary positive strand to serve as mRNA. Viruses are obligate parasites that are completely dependant on the host cell for the replication and transcription of their genomes as well as the translation of the mRNA transcripts into proteins. Viral proteins usually have a structural function, making up a shell around the genome, but may contain some enzymes that are necessary for the virus replication and life cycle in the host cell. Both bacterial virus (bacteriophages) and animal viruses play an important role as tools in molecular and cellular biology research.

Viruses are classified in two families depending on whether they have RNA or DNA genomes and whether these genomes are double or single stranded. Further subdivision into types takes into account whether the genome consists of a single RNA molecule or many molecules as in the case of segmented viruses. Four types of bacteriophages are widely used in biochemical and genetic research. These are the T phages, the temperate phages typified by bacteriophage lambda, the small DNA phages like M13, and the RNA phages. Animal viruses are subdivided in many classes and types. Class I viruses contain a single molecule of double stranded DNA and are exemplified by adenovirus, simian virus 40 (SV40), herpes viruses and human papilloma viruses. Class II viruses are also called parvoviruses and are made of single stranded DNA that is copied in to double stranded DNA before transcription in the host cell. Class III viruses are double stranded RNA viruses that have segmented genomes which means that they contain 10–12 separate double stranded RNA molecules. The negative strands serve as template for mRNA synthesis. Class IV viruses, typified by poliovirus, have single plus strand genomic RNA that serves as the mRNA. Class V viruses contain a single negative strand RNA which serves as the template for the production of mRNA by specific virus enzymes. Class VI viruses are also known as retroviruses and contain double stranded RNA genome. These viruses have an enzyme called reverse transcriptase that can both copy minus strand DNA from genomic RNA catalyze the synthesis of a complementary plus DNA strand. The resulting double stranded DNA is integrated in the host chromosome and is transcribed by the host own machinery. The resulting transcripts are either used to synthesize proteins or produce new viral particles. These new viruses are released by budding, usually without killing the host cell. Both HIV and HTLV viruses belong to this class of viruses.

Virus genetics are studied by either investigating genome mutations or exchange of genetic material during the life cycle of the virus. The frequency and types of genetic variations in the virus are influenced by the nature of the viral genome and its structure. Especially important are the type of the nucleic acid that influence the potential for the viral genome to integrate in the host, and the segmentation that influence exchange of genetic information through assortment and recombination .

Mutations in the virus genome could either occur spontaneously or be induced by physical and chemical means. Spontaneous mutations that arise naturally as a result of viral replication are either due to a defect in the genome replication machinery or to the incorporation of an analogous base instead of the normal one. Induced virus mutants are obtained by either using chemical mutants like nitrous oxide that acts directly on bases and modify them or by incorporating already modified bases in the virus genome by adding these bases as substrates during virus replication. Physical agents such as ultra-violet light and x rays can also be used in inducing mutations. Genotypically, the induced mutations are usually point mutations, deletions, and rarely insertions. The phenotype of the induced mutants is usually varied. Some mutants are conditional lethal mutants. These could differ from the wild type virus by being sensitive to high or low temperature. A low temperature mutant would for example grow at 88°F (31°C) but not at 100°F (38°C), while the wild type will grow at both temperatures. A mutant could also be obtained that grows better at elevated temperatures than the wild type virus. These mutants are called hot mutants and may be more dangerous for the host because fever, which usually slows the growth of wild type virus, is ineffective in controlling them. Other mutants that are usually generated are those that show drug resistance, enzyme deficiency, or an altered pathogenicity or host range. Some of these mutants cause milder symptoms compared to the parental virulent virus and usually have potential in vaccine development as exemplified by some types of influenza vaccines.

Besides mutation, new genetic variants of viruses also arise through exchange of genetic material by recombination and reassortment. Classical recombination involves the breaking of covalent bonds within the virus nucleic acid and exchange of some DNA segments followed by rejoining of the DNA break. This type of recombination is almost exclusively reserved to DNA viruses and retroviruses. RNA viruses that do not have a DNA phase rarely use this mechanism. Recombination usually enables a virus to pick up genetic material from similar viruses and even from unrelated viruses and the eukaryotic host cells. Exchange of genetic material with the host is especially common with retroviruses. Reassortment is a non-classical kind of recombination that occurs if two variants of a segmented virus infect the same cell. The resulting progeny virions may get some segments from one parent and some from the other. All known segmented virus that infect humans are RNA viruses. The process of reassortment is very efficient in the exchange of genetic material and is used in the generation of viral vaccines especially in the case of influenza live vaccines. The ability of viruses to exchange genetic information through recombination is the basis for virus-based vectors in recombinant DNA technology and hold great promises in the development of gene therapy. Viruses are attractive as vectors in gene therapy because they can be targeted to specific tissues in the organs that the virus usually infect and because viruses do not need special chemical reagents called transfectants that are used to target a plasmid vector to the genome of the host.

Genetic variants generated through mutations, recombination or reassortment could interact with each other if they infected the same host cell and prevent the appearance of any phenotype . This phenomenon, where each mutant provide the missing function of the other while both are still genotypically mutant, is known as complementation. It is used as an efficient tool to determine if mutations are in unique or in different genes and to reveal the minimum number of genes affecting a function. Temperature sensitive mutants that have the same mutation in the same gene will for example not be able to complement each other. It is important to distinguish complementation from multiplicity reactivation where a higher dose of inactivated mutants will be reactivated and infect a cell because these inactivated viruses cooperate in a poorly understood process. This reactivation probably involves both a complementation step that allows defective viruses to replicate and a recombination step resulting in new genotypes and sometimes regeneration of the wild type. The viruses that need complementation to achieve an infectious cycle are usually referred to as defective mutants and the complementing virus is the helper virus. In some cases, the defective virus may interfere with and reduce the infectivity of the helper virus by competing with it for some factors that are involved in the viral life cycle. These defective viruses called "defective interfering" are sometimes involved in modulating natural infections. Different wild type viruses that infect the same cell may exchange coat components without any exchange of genetic material. This phenomenon, known as phenotypic mixing is usually restricted to related viruses and may change both the morphology of the packaged virus and the tropism or tissue specificity of these infectious agents.

See also Viral vectors in gene therapy; Virology; Virus replication; Viruses and responses to viral infection

Viruses

Viruses are infectious agents that have no organelles or reproductive machinery of their own. Viruses cannot duplicate their DNA or RNA, nor can they translate their genetic information into protein. Essentially, they are small bags of genes that typically encode a comparatively small number of proteins. For example, the human immunodeficiency virus (HIV) is composed of only nine genes, yet with these simple nine bits of protein it can wreak havoc on the human immune system. Others, such as herpes simplex or adenovirus, can have large genomes with dozens of genes. Simple or complex, though, all viruses have the same function. As they cannot make protein or reproduce on their own, viruses must force bacteria or animal cells to do their work for them. A virus is, simply put, a genetic parasite.

As it does not have to sustain other energetically expensive cellular processes, a virus has a very simple structure. It is usually composed of nucleic acids (DNA or RNA) and a protein coat. This coat may be a very primitive covering (called a capsid) or it may be a complex structure derived from a host's membrane (called an envelope). Viral envelopes may possess a variety of receptors and decoys designed to fool the host's immune system. Avoiding detection is one of a virus's main tasks, and viruses may rely on dummy surface molecules or manipulating the immune system to do so. For example, HIV convinces infected cells to stop producing molecular flags that indicate infection to the rest of the body. In order to be successful, a virus must defeat the immune system and reproduce itself efficiently.

A viral life cycle generally has five distinct phases:

1. Attachment: The virus must connect itself to the target cell. Often, this is accomplished by molecules on the virus that mimic cell surface receptors required to interact with other cells. Rhinoviruses, some of which cause the common cold, bind to intercellular adhesion molecules (ICAMs) on the respiratory tract. ICAMs are meant to help white blood cells find their targets, but rhinoviruses have evolved to use them to get into cells. HIV binds to CD4 and CCR5, two surface markers involved in T-cell trafficking. Such binding may restrict the virus to infecting certain species or certain types of cells within a species.
2. Penetration: Once docked, the virus must get its nucleic material inside the cell. Some viruses are taken entirely into the cell. Others inject their DNA or RNA through the cell membrane. Still others fuse their membrane with their hosts' and dump the nuclear contents into the cytosol. In order for the virus to use the host's reproduction capabilities, it needs to be inside the cell.
3. Replication: Once the nucleic acids are inside, the virus will use the host's replication machinery to make more copies of itself. Some viruses, such as HIV, are made of RNA instead of DNA. For this reason, these viruses must first transcribe their genomes into DNA in order for cells to copy them. Whether made of DNA or RNA, though, a virus will also force the host cell to make its protein coat and any other proteins necessary to put the virus together. Rather than expending its precious energy on maintenance, the host cell instead is forced to use its energy to make viral parts.
4. Assembly: The various parts of the virus are put together with its freshly copied DNA. Soon the host cell is full of these virions, or individual viral particles, and the virions are ready to infect another cell.
5. Lysis: The virus ruptures the cell and disperses its viral progeny, all off to infect new host cells and begin the cycle again.

Not all viruses lyse (rupture) their host cells. Some may bud off the host cell. Others may become latent and rest in the host's cytosol or even the host's own chromosomes for a long time without causing damage. For example, herpes simplex 1 infects individuals and causes cold sores, but does so only intermittently. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), also known as mononucleosis, both infect the human body and remain latent for life. These viruses are held in check by the immune system and cause no harm, but they never go away completely. Persons with acquired immune deficiency syndrome (AIDS) lose immune function, and CMV and EBV have been known to resurface in persons with AIDS.

Because some viruses insert themselves into the host's genome, there is a possibility that they might affect normal gene regulation in the host itself. Viruses can be responsible for certain cellular problems that involve gene regulation. For example, some viruses are thought to be the cause of certain types of cancer. Human papilloma virus, for example, has been associated with cervical cancer. Hepatitis B and hepatitis C cause a majority of the world's cases of liver cancer.

While viruses can be specific for a particular species, cross-species infection happens frequently and sometimes with disastrous results. For example, all fifteen known strains of influenza A virus reside in aquatic birds, preferring the intestinal tracts of ducks in particular. As such, fowl fecal matter, as well as seals, whales, pigs, horses, and chickens, have been implicated in a number of human influenza outbreaks.

As a parasite, the best evolutionary strategy for a virus is for it not to harm the host. It is thought that HIV-1 and HIV-2 were introduced to humanity through the ingestion of uncooked monkeys (a chimpanzee and a sooty mangabey, respectively) sometime in the early twentieth century. These monkeys had been infected with simian immunodeficiency virus (SIV), which is fairly benign to its host. In species such as the mangabeys, African green monkeys, and pigtailed macaques, SIV causes no detectable problems and infection is widespread (it is estimated that some 80 percent of captive sooty mangabeys carry the disease). Infected rhesus monkeys, however, lose their ability to fight disease and waste away. Likewise, when the virus mutated to HIV in humans, it infected human populations and continues to cause widespread sickness and death. If HIV is to be with humanity for a long time, then it must become a little less virulent, lest it kill off all of its hosts.

see also Animal Testing.

Ian Quigley

Bibliography

Cann, Alan J., ed. DNA Virus Replication. New York: Oxford University Press, 2000.

Dalgleish, Angus, and Robin Weiss. HIV and the New Virus. San Diego: Academic, 1999.

Johnson, George B. Biology: Visualizing Life. New York: Holt, Rinehart and Winston, Inc., 1998.

Virology, viral classification, types of viruses

Virology is the discipline of microbiology that is concerned with the study of viruses . Viruses are essentially nonliving repositories of nucleic acid that require the presence of a living prokaryotic or eukaryotic cell for the replication of the nucleic acid.

Scientists who make virology their field of study are known as virologists. Not all virologists study the same things, as viruses can exist in a variety of hosts. Viruses can infect animals (including humans), plants, fungi , birds, aquatic organisms, protozoa , bacteria , and insects. Some viruses are able to infect several of these hosts, while other viruses are exclusive to one host.

All viruses share the need for a host in order to replicate their deoxyribonucleic acid (DNA ) or ribonucleic acid (RNA ). The virus commandeers the host's existing molecules for the nucleic acid replication process. There are a number of different viruses. The differences include the disease symptoms they cause, their antigenic composition, type of nucleic acid residing in the virus particle, the way the nucleic acid is arranged, the shape of the virus, and the fate of the replicated DNA. These differences are used to classify the viruses and have often been the basis on which the various types of viruses were named.

The classification of viruses operates by use of the same structure that governs the classification of bacteria. The International Committee on Taxonomy of Viruses established the viral classification scheme in 1966. From the broadest to the narrowest level of classification, the viral scheme is: Order, Family, Subfamily, Genus, Species, and Strain/type. To use an example, the virus that was responsible for an outbreak of Ebola hemorrhagic fever in a region of Africa called Kikwit is classified as Order Mononegavirales, Family Filoviridae, Genus Filovirus, and Species Ebola virus Zaire.

In the viral classification scheme, all families end in the suffix viridae , for example Picornaviridae. Genera have the suffix virus . For example, in the family Picornaviridae there are five genera: enterovirus, cardiovirus, rhinovirus, apthovirus, and hepatovirus. The names of the genera typically derive from the preferred location of the virus in the body (for those viral genera that infect humans). As examples, rhinovirus is localized in the nasal and throat passages, and hepatovirus is localized in the liver. Finally, within each genera there can be several species.

As noted above, there are a number of criteria by which members of one grouping of viruses can be distinguished from those in another group. For the purposes of classification, however, three criteria are paramount. These criteria are the host organism or organisms that the virus utilizes, the shape of the virus particle, and the type and arrangement of the viral nucleic acid.

An important means of classifying viruses concerns the type and arrangement of nucleic acid in the virus particle. Some viruses have two strands of DNA, analogous to the double helix of DNA that is present in prokaryotes such as bacteria and in eukaryotic cells. Some viruses, such as the Adenoviruses , replicate in the nucleus of the host using the replication machinery of the host. Other viruses, such as the poxviruses, do not integrate in the host genome, but replicate in the cytoplasm of the host. Another example of a double-stranded DNA virus are the Herpesviruses.

Other viruses only have a single strand of DNA. An example is the Parvoviruses. Viruses such as the Parvoviruses replicate their DNA in the host's nucleus. The replication involves the formation of what is termed a negative-sense strand of DNA, which is a blueprint for the subsequent formation of the RNA and DNA used to manufacture the new virus particles.

The genome of other viruses, such as Reoviruses and Birnaviruses, is comprised of double-stranded RNA. Portions of the RNA function independently in the production of a number of so-called messenger RNAs, each of which produces a protein that is used in the production of new viruses.

Still other viruses contain a single strand of RNA. In some of the single-stranded RNA viruses, such as Picornaviruses, Togaviruses, and the Hepatitis A virus, the RNA is read in a direction that is termed "+ sense." The sense strand is used to make the protein products that form the new virus particles. Other single-stranded RNA viruses contain what is termed a negative-sense strand. Examples are the Orthomyxoviruses and the Rhabdoviruses. The negative strand is the blueprint for the formation of the messenger RNAs that are required for production of the various viral proteins.

Still another group of viruses have + sense RNA that is used to make a DNA intermediate. The intermediate is used to manufacture the RNA that is eventually packaged into the new virus particles. The main example is the Retroviruses (the Human Immunodeficiency Viruses belong here). Finally, a group of viruses consist of double-stranded DNA that is used to produce a RNA intermediate. An example is the Hepadnaviruses .

An aspect of virology is the identification of viruses. Often, the diagnosis of a viral illness relies, at least initially, on the visual detection of the virus. For this analysis, samples are prepared for electron microscopy using a technique called negative staining, which highlights surface detail of the virus particles. For this analysis, the shape of the virus is an important feature.

A particular virus will have a particular shape. For example, viruses that specifically infect bacteria, the so-called bacteriophages, look similar to the Apollo lunar landing spacecraft. A head region containing the nucleic acid is supported on a number of spider-like legs. Upon encountering a suitable bacterial surface, the virus acts like a syringe, to introduce the nucleic acid into the cytoplasm of the bacterium.

Other viruses have different shapes. These include spheres, ovals, worm-like forms, and even irregular (pleomorphic) arrangements. Some viruses, such as the influenza virus, have projections sticking out from the surface of the virus. These are crucial to the infectious process.

As new species of eukaryotic and prokaryotic organisms are discovered, no doubt the list of viral species will continue to grow.

See also Viral genetics; Virus replication

Virus replication

Viral replication refers to the means by which virus particles make new copies of themselves.

Viruses cannot replicate by themselves. They require the participation of the replication equipment of the host cell that they infect in order to replicate. The molecular means by which this replication takes place varies, depending upon the type of virus.

Viral replication can be divided up into three phases: initiation, replication, and release.

The initiation phase occurs when the virus particle attaches to the surface of the host cell, penetrates into the cell and undergoes a process known as uncoating, where the viral genetic material is released from the virus into the host cell's cytoplasm . The attachment typically involves the recognition of some host surface molecules by a corresponding molecule on the surface of the virus. These two molecules can associate tightly with one another, binding the virus particle to the surface. A well-studied example is the haemagglutinin receptor of the influenzae virus. The receptors of many other viruses have also been characterized.

A virus particle may have more than one receptor molecule, to permit the recognition of different host molecules, or of different regions of a single host molecule. The molecules on the host surface that are recognized tend to be those that are known as glycoproteins. For example, the human immunodeficiency virus recognizes a host glycoprotein called CD4. Cells lacking CD4 cannot, for example, bind the HIV particle.

Penetration of the bound virus into the host interior requires energy. Accordingly, penetration is an active step, not a passive process. The penetration process can occur by several means. For some viruses, the entire particle is engulfed by a membrane-enclosed bag produced by the host (a vesicle) and is drawn into the cell. This process is called endocytosis. Polio virus and orthomyxovirus enters a cell via this route. A second method of penetration involves the fusion of the viral membrane with the host membrane. Then the viral contents are directly released into the host. HIV, paramyxoviruses, and herpes viruses use this route. Finally, but more rarely, a virus particle can be transported across the host membrane. For example, poliovirus can cause the formation of a pore through the host membrane. The viral DNA is then released into the pore and passes across to the inside of the host cell.

Once inside the host, the viruses that have entered via endocytosis or transport across the host membrane need to release their genetic material. With poxvirus, viral proteins made after the entry of the virus into the host are needed for uncoating. Other viruses, such as adenoviruses , herpesviruses, and papovaviruses associate with the host membrane that surrounds the nucleus prior to uncoating. They are guided to the nuclear membrane by the presence of so-called nuclear localization signals, which are highly charged viral proteins. The viral genetic material then enters the nucleus via pores in the membrane. The precise molecular details of this process remains unclear for many viruses.

For animal viruses, the uncoating phase is also referred to as the eclipse phase. No infectious virus particles can be detected during that 10–12 hour period of time.

In the replication, or synthetic, phase the viral genetic material is converted to deoxyribonucleic acid (DNA), if the material originally present in the viral particle is ribonucleic acid (RNA ). This so-called reverse transcription process needs to occur in retroviruses , such as HIV. The DNA is imported into the host nucleus where the production of new DNA, RNA, and protein can occur. The replication phase varies greatly from virus type to virus type. However, in general, proteins are manufactured to ensure that the cell's replication machinery is harnessed to permit replication of the viral genetic material, to ensure that this replication of the genetic material does indeed occur, and to ensure that this newly made material is properly packaged into new virus particles.

Replication of the viral material can be a complicated process, with different stretches of the genetic material being transcribed simultaneously, with some of these gene products required for the transcription of other viral genes. Also replication can occur along a straight stretch of DNA, or when the DNA is circular (the so-called "rolling circle" form). RNA-containing viruses must also undergo a reverse transcription from DNA to RNA prior to packaging of the genetic material into the new virus particles.

In the final stage, the viral particles are assembled and exit the host cell. The assembly process can involve helper proteins, made by the virus or the host. These are also called chaperones . Other viruses, such as tobacco mosaic virus , do not need these helper chaperones, as the proteins that form the building blocks of the new particles spontaneously self-assemble. In most cases, the assembly of viruses is symmetrical; that is, the structure is the same throughout the viral particle. For example, in the tobacco mosaic virus, the proteins constituents associate with each other at a slight angle, producing a symmetrical helix. Addition of more particles causes the helix to coil "upward" forming a particle. An exception to the symmetrical assembly is the bacteriophage . These viruses have a head region that is supported by legs that are very different in structure. Bacteriophage assembly is very highly coordinated, involving the separate manufacture of the component parts and the direct fitting together of the components in a sequential fashion.

Release of viruses can occur by a process called budding. A membrane "bleb" containing the virus particle is formed at the surface of the cell and is pinched off. For herpes virus this is in fact how the viral membrane is acquired. In other words, the viral membrane is a host-derived membrane. Other viruses, such as bacteriophage, may burst the host cell, spewing out the many progeny virus particles. But many viruses do not adopt such a host destructive process, as it limits the time of an infection due to destruction of the host cells needed for future replication.

See also Herpes and herpes virus; Human immunodeficiency virus (HIV); Invasiveness and intracellular infection

Epidemics, viral

An epidemic is an outbreak of a disease that involves a large number of people in a contained area (e.g., village, city, country). An epidemic that is worldwide in scope is referred to as a pandemic. A number of viruses have been responsible for epidemics . Some of these have been present since antiquity, while others have emerged only recently.

Smallpox is an example of an ancient viral epidemic. Outbreaks of smallpox were described in 1122 B.C. in China. In A.D. 165, Roman Legionnaires returning from military conquests in Asia and Africa spread the virus to Europe. One third of Europe's population died of smallpox during the 15-year epidemic. Smallpox remained a scourge until the late eighteenth century. Then, Edward Jenner devised a vaccine for the smallpox virus, based on the use of infected material from cowpox lesions. Less than a century later, naturally occurring smallpox epidemics had been ended.

Influenza is an example of a viral epidemic that also has its origins in ancient history. In contrast to smallpox, influenza epidemics remain a part of life today, even with the sophisticated medical care and vaccine development programs that can be brought to bear on infections.

Epidemics of influenza occurred in Europe during the Middle Ages. By the fifteenth century, epidemics began with regularity. A devastating epidemic swept through Spain, France, the Netherlands, and the British Isles in 1426–1427. Major outbreaks occurred in 1510, 1557, and 1580. In the eighteenth century there were three to five epidemics in Europe. Three more epidemics occurred in the nineteenth century. Another worldwide epidemic began in Europe in 1918. American soldiers returning home after World War I brought the virus to North America. In the United States alone almost 200,000 people died. The influenza epidemic of 1918 ranks as one of the worst natural disasters in history. In order to put the effects of the epidemic into perspective, the loss of life due to the four years of conflict of World War I was 10 million. The death toll from influenza during 5 months of the 1918 epidemic was 20 million.

Epidemics of influenza continue to occur. Examples include epidemics of the Asian flu (1957), and the Hong Kong flu (1968). Potential epidemics due to the emergence of new forms of the virus in 1976 (the Swine flu) and 1977 (Russian flu) failed to materialize.

The continuing series of influenza epidemics is due to the ability of the various types of the influenza virus to alter the protein composition of their outer surface. Thus, the antibodies that result from an influenza epidemic in one year may be inadequate against the immunologically distinct influenza virus that occurs just a few years later. Advances in vaccine design and the use of agents that lessen the spread of the virus are contributing to a decreased scope of epidemics. Still, the threat of large scale influenza epidemics remains.

In the twentieth century, new viral epidemics have emerged. A number of different viruses have been grouped together under the designation of hemorrhagic fevers . These viruses are extremely contagious and sweep rapidly through the affected population. A hallmark of such infections is the copious internal bleeding that results from the viral destruction of host tissue. Death frequently occurs. The high death rate in fact limits the scope of these epidemics. Essentially the virus runs out of hosts to infect. The origin of hemorrhagic viruses such as the Ebola virus is unclear. A developing consensus is that the virus periodically crosses the species barrier from its natural pool in primates.

Another viral epidemic associated with the latter half of the twentieth century is acquired immunodeficiency syndrome. This debilitating and destructive disease of the immune system is almost certainly caused by several types of a virus referred to as the Human Immunodeficiency Virus (HIV ). The first known death due to HIV infection was a man in the Congo in 1959. The virus was detected in the United States only in 1981. Subsequent examination of stored blood sample dating back 40 years earlier revealed the presence of HIV.

HIV may have arisen in Africa, either from a previously unknown virus, or by the mutation of a virus resident in a non-human population (e.g., primates). The tendency of the virus to establish a latent infection in the human host before the appearance of the symptoms of an active infection make it difficult to pinpoint the origin of the virus. Moreover, this aspect of latency, combined with the ready ability of man to travel the globe, contributes to the spread of the epidemic. Indeed, the epidemic may now be more accurately considered to be a pandemic.

A final example of a twentieth century viral epidemic is that caused by the Hanta virus. The virus causes a respiratory malady that can swiftly overwhelm and kill the patient. The virus is normally resident on certain species of mouse. In the mid-1990s, an epidemic of Hanta virus syndrome occurred in native populations in the Arizona and New Mexico areas of the United States west. As with other viral epidemics, the epidemic faded away as quickly as it had emerged. However, exposure of someone to the mouse host or to dried material containing the virus particles can just as quickly fuel another epidemic.

Given their history, it seems unlikely viral epidemics will be eliminated. While certain types of viral agents will be defeated, mainly by the development of effective vaccines and the undertaking of a worldwide vaccination program (e.g., smallpox), other viral diseases will continue to plague mankind.

See also AIDS; Hemorrhagic fevers and diseases; Virology

Viral vectors in gene therapy

Gene therapy is the introduction of a gene into cells to reverse a functional defect caused by a defect in a host genome (the set of genes present in an organism).

The use of viruses quickly became an attractive possibility once the possibility of gene therapy became apparent. Viruses require other cells for their replication. Indeed, an essential feature of a virus replication cycle is the transfer of their genetic material (deoxyribonucleic acid , DNA ; or ribonucleic acid , RNA ) into the host cell, and the replication of that material in the host cell. By incorporating other DNA or RNA into the virus genome, the virus then becomes a vector for the transmission of that additional genetic material. Finally, if the inserted genetic material is the same as a sequence in the host cell that is defective, then the expression of the inserted gene will provide the product that the defective host genome does not. As a result, host defective host genetic function and the consequences of the defects can be reduced or corrected.

Retroviruses contain RNA as the genetic material. A viral enzyme called reverse transcriptase functions to manufacture DNA from the RNA, and the DNA can then become incorporated into the host DNA. Despite the known involvement of some retroviruses in cancer, these viruses are attractive for gene therapy because of their pronounced tendency to integrate the viral DNA into the host genome. Retroviruses used as gene vectors also have had the potential cancer-causing genetic information deleted. The most common retrovirus that has been used in experimental gene therapy is the Moloney murine leukaemia virus. This virus can infect cells of both mice and humans. This makes the results obtained from mouse studies more relevant to humans.

Adenoviruses are another potential gene vector. Once they have infected the host cell, many rounds of DNA replication can occur. This is advantageous, as much of the therapeutic product could be produced. However, because integration of the virally transported gene does not occur, the expression of the gene only occurs for a relatively short time. To produce levels of the gene product that would have a substantial effect on a patient, the virus vector needs to administered repeatedly. As for retroviruses, the adenoviruses used as vectors need to be crippled so as to prevent the production of new viruses.

Adenovirus vector has been used to correct mutations the gene that is defective in cystic fibrosis. However, as of May 2002, the success rate in human trials remained low. In addition, the immune response to the high levels of the vector that are needed can be problematic.

Another important aspect of gene therapy concerns the target of the viral vectors. The viruses need to be targeted at host cells that are actively dividing, because only in cells in which DNA replication is occurring will the inserted viral genetic material be replicated. This is one reason why cancers are a conceptually attractive target of virus-mediated gene therapy, as cancerous cells are dangerous by virtue of their rapid and uncontrolled division.

Cancerous cells arise by some form of mutation. Therefore, therapy to replace defective genes with functional genes holds promise for cancer researchers. The target of gene therapy can vary, as many cancers have mutations that direct a normal cell towards acquiring the potential to become cancerous, and other mutations that inactivate mechanisms that function to regulate growth control. Furthermore, gene therapy can be directed at the immune system rather than directly at the cancerous cell. An example of this strategy is known as immunopotentiation (the enhancement of the immune response to cancers).

A risk of viral gene therapy, in those viruses that operate by integrating genetic material into the host genome, is the possibility of damage to the host DNA by the insertion. Alteration of some other host gene could have unforeseen and undesirable side effects. The elimination of this possibility will require further technical refinements. Adenoviruses are advantageous in this regard as the replication of their DNA in the host cell does not involve insertion of the viral DNA into the host DNA. Accordingly, the possibility of mutations due to insertion do not exist.

The September 1999 death of an 18 year old patient with a rare metabolic condition, who died while receiving viral gene therapy, considerably slowed progress on clinical applications of viral gene therapy.

See also Biotechnology

Cold, viruses

The cold is one of the most common illnesses of humans. In the Unites States alone, there are more than one billion colds each year. Typically a cold produces sneezing, scratchy throat, and a runny nose for one or two weeks. The causes of the common cold are viruses.

More than 200 different viruses can cause a cold. Rhinoviruses account for anywhere from 35% to over half of all colds, particularly in younger and older people. This has likely been the case for millennia. Indeed, the name Rhinovirus is from the Greek word rhin, meaning, "nose." There are over one hundred different types of Rhinovirus, based on the different proteins that are on the surface of the virus particle. Rhinovirus belongs to the virus family Picornaviridae. The genetic material of the virus is ribonucleic acid (RNA ) and the genome is of a very small size.

Rhinovirus is spread from one person to another by "hand to hand" contact, that is, by physical contact or from one person sneezing close by another person. The virus needs to inside the human body to be able to replicate. The internal temperature of the body, which is normally between 97–99°F (36.1–37.2° C) is perfect for Rhinovirus. If the temperature varies only a few degrees either way of the window, the virus will not replicate.

Rhinovirus has been successful in causing colds for such as long time because of the large number of antigenic types of the virus that exist. Producing a vaccine against the virus would require the inclusion of hundreds of antibodies to the hundreds of different possible antigens. This is not practical to achieve. Furthermore, not all the Rhinovirus antigens that are important in generating a cold are exposed at the surface. So, even if a corresponding antibody were present, neutralization of the antigen via the binding of the antibody with the antigen would not occur. Another factor against vaccine development is the difficulty in being able to grow Rhinovirus in the laboratory.

Another virus that causes colds are members of the Coronavirus family. The name of the virus derives from the distinctive flexible shape and appearance of the virus particle. Surface projections give the virus a crown-like, or corona, appearance. There are more than 30 known strains of Coronavirus. Of these, three or four from the genus Coronavirus can infect humans. Cattle, pigs, rodents, cats, dogs, and birds are also hosts. Members of the genus Torovirus can also cause gastroenteritis .

Coronavirus has been known since 1937, when it was isolated from chickens. It was suspected of being a cause of colds, but this could not be proven until the 1960s, when techniques to grow the virus in laboratory cultures were devised. Like Rhinovirus, Coronavirus also contains RNA. However, in contrast to the same amount of genetic material carried in Rhinoviruses, the genome of the Coronavirus is the largest of all the RNA-containing viruses.

Other viruses account for 10–15% of colds in adults. These adenoviruses , coxsackieviruses, echoviruses, orthomyxoviruses (including the influenza A and B viruses), paramyxoviruses, respiratory syncytial virus and enteroviruses can also cause other, more severe illnesses.

Aside from vaccines, various "home remedies" to the common cold exist. Larger than normal doses of Vitamin C have been claimed to lessen the symptoms or prevent the common cold. The evidence for this claim is still not definitive. Another remedy, mythologized as an example of a mother's care for her children, is chicken soup. Studies have demonstrated that chicken soup may indeed shorten the length of a cold and relieve some of the symptoms. The active ingredient(s), if any, that are responsible are not known, however. For now, the best treatment for a cold is to attempt to relieve the symptoms via such home remedies and over the counter medications. Nasal decongestants decrease the secretions from the nose and help relieve congestion. Antihistamines act to depress the histamine allergic response of the immune system . This has been claimed to help relieve cold symptoms. Analgesics relieve some of pain and fever associated with a cold.

Some so-called alternative medications may have some benefit. For example, lozenges composed of zinc can sometimes reduce the duration of the common cold, perhaps due to the need for zinc by the immune system. Echinacea is known to stimulate white blood cell activity.

See also Virology

Viral Diseases

In order to understand viral infections, one must understand a little about how a virus functions. All viruses are obligate parasites ; that is, they depend on a "host" to survive and reproduce. In the case of a virus, the host is the cell of a living organism. Outside of a host cell, viruses are inert molecules, waiting to attach to a victim cell. Although viruses contain genetic material (either deoxyribonucleic acid [DNA] or ribonucleic acid [RNA]), they lack the internal machinery (organelles) to produce proteins from the information contained in their own genetic code . The simplest virus contains only three genes.

A viral infection begins when a virus inserts its genetic material into a host cell. First, the virus attaches to a specific structure on the cell's surface via an attachment protein. Depending on the virus, either the genetic material diffuses into the host cell or the entire virus enters the cell. The poliomyelitis virus may have over one million copies of its basic genetic information (RNA) inside a single, infected human intestinal mucosal cell.

One or more of the genes on the viral genetic material code for enzymes that essentially "hijack" the host cell, causing it to produce only viral parts, which are then assembled into copies of the virus within the host cell. These viral copies are released, leaving the cell either by a process called "budding" (where just one or a few viruses leave the cell at a time) or by a process called lysis (where the cellular membrane ruptures and releases all of the virus particles at once). Both processes usually kill the host cell. The new viruses then infect surrounding cells, continuing the process. Examples of diseases that are viral in origin are influenza (swine flu), some types of pneumonia, poliomyelitis, cold sores and shingles, and AIDS (acquired immunodeficiency syndrome).

Of course, host cells have several defenses against the viral attacks. For example, in animals (including humans), viral infection leads to the synthesis and secretion of proteins called interferons , which "interfere" with viral replication by helping adjacent uninfected cells become resistant to infection. Often, this is not enough to stop the spread of infection, and the body's immune system can cause fever, achiness, tiredness, and other defenses, making the person feel "sick" but acting to help the body fight off the attack. Eventually, the virus is completely removed, and the symptoms subside.

HIV (human immunodeficiency virus) is an exception to this situation because HIV infects cells of the immune system that are necessary to kill the infected cells. So, although HIV does not itself directly cause the condition known as AIDS, the eventual death of immune cells allows other infections to spread (called secondary infections).

The first outbreaks of the paralyzing poliomyelitis (polio) virus in the United States occurred in the early nineteenth century. It reached its peak in 1952 when more than 21,000 people were infected. Due to the effective use of vaccines, the incidence of polio declined rapidly; the last documented transmission of the virus in the United States was 1979.

So far, no agents have been identified that are secreted by a cell that actually kills a virus. Although antibiotics are effective against bacteria, they do not kill viruses. Recently, there have been agents called antivirals designed in the laboratory and isolated from natural sources that are being used to fight certain viral infections. For example, protease inhibitors are used to inhibit the replication of HIV.

see also AIDS; Disease; DNA Viruses; Retrovirus; Sexually Transmitted Diseases; Virus

Carl J. Shuster

Bibliography

Crawford, Dorothy H. The Invisible Enemy: A Natural History of Viruses. New York: Oxford University Press, 2000.

Voyles, Bruce A. The Biology of Viruses. New York: McGraw-Hill, 1993.

Viral Infections

How Are Viruses Different from Bacteria?

How Do Viruses Infect the Body?

How Long Do Viral Infections Last?

How Do Viruses Cause Illness?

How Are Viral Infections Diagnosed and Treated?

How Are Viral Infections Prevented?

Viral infections occur when viruses enter cells in the body and begin reproducing, often causing illness. Viruses are tiny germs that can reproduce only by invading a living cell.

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Infection

Polymerase chain reaction

Virology

How Are Viruses Different from Bacteria?

Viruses are far smaller than bacteria. They are so small that they could not be seen until the electron microscope was invented in the 1940s. Unlike most bacteria, viruses are not complete cells that can function on their own. They cannot convert carbohydrates to energy, the way that bacteria and other living cells do. Viruses depend on other organisms for energy. And viruses cannot reproduce unless they get inside a living cell. Most viruses consist only of tiny particles of nucleic acid (the material that makes up genes) surrounded by a coat of protein. Some have an outer envelope as well.

Are Viruses Alive?

It would seem to be a simple matter to tell if something is alive. But biologists disagree on whether viruses are a form of life.

Viruses lack certain features that other forms of life have. They cannot convert carbohydrates, proteins, or fats into energy, a process called metabolism. They cannot reproduce on their own, but must enter a living cell and use the host cell’s energy. On the other hand, like all life forms, viruses do have genes made of nucleic acid that contain the information they need to reproduce.

Biologists have an elaborate way of classifying every form of life. Each is grouped into a kingdom (such as the Animal Kingdom) and smaller subcategories called the phylum, class, genus, and species.

Bacteria and fungi each have a kingdom of their own, but viruses are left out of this system. Many biologists think that, unlike the forms of life grouped into kingdoms, viruses did not evolve (develop) as a group. Instead, viruses may have developed individually from the kind of cells they now infect— animal cells, plant cells, or bacteria.

Thousands Of viruses

There are thousands of viruses, and in humans they cause a wide range of diseases. For instance, rhinoviruses cause colds, influenza viruses cause flu, adenoviruses cause various respiratory problems, and rotaviruses cause gastroenteritis. Polioviruses can make their way to the spinal cord and cause paralysis, while coxsackieviruses (sometimes written as Coxsackie viruses) and echoviruses sometimes infect the heart or the membranes surrounding the spinal cord or lungs. Herpesviruses cause cold sores, chickenpox, and genital herpes, a sexually transmitted disease. Other viruses cause a variety of conditions from measles and mumps to AIDS.

The body’s defense system

Most viruses do not cause serious diseases and are killed by the body’s immune system—its network of natural defenses. In many cases, people never even know they have been infected. But unlike bacteria, which can be killed by antibiotics, most viruses are not affected by existing medicines. Fortunately, scientists have been able to make vaccines, which help the body develop natural defenses to prevent many viral infections.

How Do Viruses Infect the Body?

Viruses can enter the human body through any of its openings, but most often they use the nose and mouth. Once inside, the virus attaches itself to the outside of the kind of cell it attacks, called a host cell. For example, a rhinovirus attacks cells in the nose, while an enterovirus binds to cells in the stomach and intestines. Then the virus works its way through the host cell’s outer membrane.

After entering the cell, the virus begins making identical viruses from the host cell’s protein. These new viruses may make their way back out through the host cell’s membrane, sometimes destroying the cell, and then attacking new host cells. This process continues until the body develops enough antibodies* and other defenses to defeat the viral invaders.

* antibodies

are proteins made by the body’s immune system to target a specific kind of germ or other foreign substance.

Not all viruses attack only one part of the body, causing what is called a localized infection. Some viruses spread through the bloodstream or the nerves, attacking cells throughout the body. For instance, HIV, the human immunodeficiency virus that causes AIDS, attacks certain cells of the immune system that are located throughout the body.

How Long Do Viral Infections Last?

In most types of viral infection, the immune system clears the virus from the body within days to a few weeks. But some viruses cause persistent or latent* infections, which can last for years. In these cases, a person may get infected and seem to recover or may not be aware of being infected at all. Then years later, the illness will occur again, or symptoms will start for the first time. Viruses that can cause latent infections include herpesviruses, Hepatitis B and C viruses, and HIV.

* latent

infections are dormant or hidden illnesses that do not show the signs and symptoms of active diseases.

How Do Viruses Cause Illness?

Viruses can cause illness by destroying or interfering with the functioning of large numbers of important cells. Sometimes, as mentioned earlier, the cell is destroyed when the newly created viruses leave it. Sometimes the virus keeps the cell from producing the energy it needs to live, or the virus upsets the cell’s chemical balance in some other way. Sometimes the virus seems to trigger a mysterious process called “programmed cell death” or apoptosis (ap-op-TO-sis) that kills the cell.

Some persistent or latent viral infections seem to transform cells into a cancerous state that makes them grow out of control. It has been estimated that 10 to 20 percent of cancers are caused by viral infections. The most common are liver cancer caused by persistent infection with Hepatitis B or Hepatitis C virus, and cancer of the cervix (the bottom of a woman’s uterus or womb), linked to certain strains of the human papillomavirus.

Sometimes a viral illness is caused not by the virus itself, but by the body’s reaction to it. The immune system may kill cells in order to get rid of the virus that is inside them. This can cause serious illness if the cells being killed are very important to the body’s functioning, like those in the lungs or central nervous system, or if the cells cannot reproduce quickly enough to replace the ones being destroyed.

What Is a 24-Hour Virus?

When people have a mild illness— perhaps fever and an upset stomach, perhaps nausea and diarrhea—they often say they have a “24-hour virus” or a “stomach virus.” Many viruses can cause these kinds of symptoms, but there are many other possible causes as well, including bacterial infection or bacterial food poisoning. People usually recover from these brief or mild illnesses before doctors can do the tests that determine the causes. So a “stomach virus” may or may not be a virus at all.

How Are Viral Infections Diagnosed and Treated?

Symptoms

Symptoms vary widely, depending on the virus and the organs involved. Many viruses, like many bacteria, cause fever, and either respiratory symptoms (coughing and sneezing) or intestinal symptoms (nausea, vomiting, diarrhea). Viral illnesses often cause high fevers in young children, even when the illnesses are not dangerous.

Diagnosis

Some viral infections, such as influenza, the common cold, and chickenpox, are easily recognized by their symptoms and no lab tests are needed. For many others, such as viral hepatitis, AIDS, and mononucleosis, a blood sample is analyzed for the presence of specific antibodies to the virus. If present, these antibodies help confirm the diagnosis. In some cases, a virus may be grown in the laboratory, using a technique called tissue culture, or identified by its nucleic acid, using a technique called polymerase chain reaction (PCR). Tests like PCR or tissue culture are used when antibody tests are not precise enough or when the actual amount of a virus in the body must be determined.

Treatment

Viruses cannot be treated with the antibiotics that kill bacteria. Fortunately, a few drugs, such as ribavirin and acyclovir, can control the spread of viral invaders without destroying host cells. Intense research to find better treatments for AIDS has led to development of many drugs that help fight the virus. Unfortunately, none of these drugs has been able to treat viral infections as effectively as antibiotics treat bacterial infections.

How Are Viral Infections Prevented?

Hygiene and sanitation

The first step in preventing the spread of viral infections is simply to practice good hygiene. This means washing the hands often, and eating only food that has been prepared properly. It also means building and maintaining facilities for getting rid of sewage safely and for providing clean drinking water.

Vaccination

Another important preventive measure is immunizing people against viruses. This involves giving people vaccines that stimulate the immune system to make antibodies, proteins that target a specific germ. Vaccines to prevent Hepatitis B, polio, mumps, measles, rubella (German measles), and chickenpox are usually given to babies and young children in the United States. Vaccines also can prevent influenza and Hepatitis A.

Vaccines are useful only against certain kinds of viruses. For example, the polioviruses that cause poliomyelitis (polio), a great crippler of children in the past, are few in number and relatively stable. So it was possible in the 1950s to make a vaccine that protects children from getting polio (although the illness still occurs in the developing world where fewer children are vaccinated). On the other hand, influenza viruses change in minor ways every few years and in a major way about every ten years, so a flu vaccine is useful for only a year or two.

One reason a vaccine for the common cold has never been developed is that there are at least a hundred different rhinoviruses that cause colds, and so far it has not been possible to make a vaccine that works against all of them. A similar problem with HIV, which has many different and fast-changing strains (variations), is one of several reasons why progress toward an AIDS vaccine has been slow.

See also

Bronchitis

Cancer

Encephalitis

Genital Warts

German Measles (Rubella)

Hepatitis

Influenza

Lassa Fever

Leukemia

Meningitis

Mumps

Polio

Rabies

Sexually Transmitted Diseases

Shingles

Warts

viral pneumonia (vy-răl) n. an acute infection of the lung caused by a virus, such as respiratory syncytial virus, adenovirus, influenza and parainfluenza viruses, or an enterovirus. It is characterized by headache, fever, muscle pain, and a cough that produces a thick sputum. The pneumonia often occurs with or subsequent to a systemic viral infection.