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Retrovirus

Retrovirus

Retroviruses are RNA-containing viruses that use the enzyme reverse transcriptase to copy their RNA into the DNA of a host cell. Retroviruses have been isolated from a variety of vertebrate species, including humans, other mammals, reptiles, and fish. The family Retroviridae includes such important human pathogens as human immunodeficiency virus (HIV) and human Tlymphotropic virus (HTLV), the causes of AIDS and adult T-cell leukemia respectively. The study of this virus family has led to the discovery of oncogenes , resulting in a quantum advance in the field of cancer genetics. Retro-viruses are also valuable research tools in molecular biology and gene therapy.

Characteristics

The classification of retroviruses is based on comparisons of the size of the genome and morphologic characteristics (see Table 1). The genomic RNA

Genus Distinguishing feature Example Host Diseases/pathologies
Alpha-retrovirus genome <8kb; assembly at cell membrane avian leukosis virus birds malignancies
Beta-retrovirus intracytoplasmic assembly mouse mammary tumor virus mice mammary and ovarian
(B- or D-type) carcinoma; lymphomas
Gamma-retrovirus genome < assembly murine leukemia virus mice malignancies
at cell membrane
Delta-retrovirus genomes < C-type bovine leukemia virus cows malignancies
Epsilon-retrovirus assembly at cell membrane; walleye dermal sarcoma virus fish solid tumors
hosts: fish
Lentivirus genome > bar-shaped human immunodeficiency virus humans immunodeficiency and
concentric core neurologic disease
Spumavirus assembly as intracyto- chimpanzee foamy spumavirus simians none apparent
plasmic particles

of retroviruses is single-stranded and possesses "positive" polarity similar to that found in messenger RNA (mRNA). Virions (virus particles) contain two 5 ("five prime"), end-linked, identical copies of the genome RNA, and are therefore said to be diploid.

Three genes are universally present in the genomes of retroviruses that are capable of replication, such as murine (mouse) leukemia virus. The gag (group antigen) gene encodes proteins that make up the nucleocapsid of the virus as well as a matrix layer, the two of which surround the RNA. The pol gene (a type of polymerase) encodes reverse transcriptase, which copies the RNA into DNA, and integrase, which integrates the DNA into the host chromosome. Depending on the species, pol can also encode protease, a protein that cleaves the initial multiprotein products of retrovirus translation to make functional proteins. Some retroviruses have incorporated viral oncogene sequences. An example of this is reticuloendotheliosis virus strain T. The genome of complex retroviruses, such as HTLV, can contain several other genes that regulate genome expression or replication and are not present in simple retroviruses.

Reverse Transcriptase

Retroviruses follow the same general steps in their replication cycles that are common to other viruses. The steps that differ from other viruses involve the retroviral reverse transcriptase, an enzyme discovered simultaneously by Howard Temin and David Baltimore in 1970. (Temin and Baltimore were awarded the Nobel Prize for this work in 1975.) Reverse transcriptase converts the single-stranded, positive-polarity RNA genome of retrovirus into double-stranded DNA, thereby reversing the typical flow of genetic information (which is from DNA to mRNA). The DNA copy is transported into the nucleus of the host cell, circularized, and integrated into the host chromosome.

This DNA copy of the retrovirus genome is referred to as the provirus or proviral DNA. The genomes of most vertebrates contain abundant numbers of incomplete and complete proviruses (endogenous retroviruses) that appear to represent remnants of past retroviral infections in germline cells. Proviruses contain structures called long terminal repeats (LTR) at each end. The LTRs contain promoter elements and transcriptional start sites that enable the retroviral genes to be expressed. They can also affect the expression of nearby cellular genes.

Retrovirus Replication Cycle

There are seven steps in the replication cycle of the retrovirus. The first step is attachment, in which the retrovirus uses one of its glycoproteins to bind to one or more specific cell-surface receptors on the host cell. Some retroviruses also employ a secondary receptor, referred to as the co-receptor. Some retroviral receptors and coreceptors have been identified. For example, CD4 and various members of the chemokine receptor family on human T cells (a type of white blood cell) serve as the HIV receptors and coreceptors.

The second and third steps are penetration and uncoating, respectively. Retroviruses penetrate the host cell by direct fusion of the virion envelope with the plasma membrane of the host. Continuation of this fusion process results in the release of the viral capsid directly into the host cell's cytoplasm, where it is partially disrupted.

Step four is replication, which occurs after the retrovirus has undergone partial uncoating. At this stage, the RNA genome is converted by reverse transcriptase into double-stranded DNA. Reverse transcriptase has three enzymatic activities: RNA-directed DNA polymerase makes one DNA strand, DNA-directed DNA polymerase makes the complementary strand, and RNAse H degrades the viral RNA strand. Reverse transcription is primed by a cellular transfer RNA (tRNA) that is packaged into retrovirus virions. It concludes with the synthesis of a double-stranded copy of the retroviral genome that is termed the "provirus," or proviral DNA.

This proviral DNA is circularized and transported to the host cell's nucleus, where it is integrated, apparently at random, into the genome by means of the retroviral enzyme called integrase. Following integration, the provirus behaves like a set of cellular genes, while the LTRs function as promoters that begin transcription back into mRNA. This transcription is carried out by RNA polymerases in the host cell. Transcription of the proviral DNA is also the means of generating progeny RNA. Viral proteins are made in the cytoplasm of the host cell by cellular ribosomes.

The next step (step five) is termed "assembly," in which retrovirus capsids are assembled in an immature form at various locations in the host cell. This is followed by an "egress" stage, in which the envelope proteins of retroviruses are acquired by budding from the plasma membrane (cell surface) of the host. Finally, step seven is "maturation." In this step, the Gag and Pol proteins of the retrovirus are cleaved by the retroviral protease, thus forming the mature and infectious form of the virus.

Consequences of Retroviral Infection

Retroviral infection can result in several different outcomes for the virus and the cell. Retroviruses are capable of inducing immunosuppressive , autoimmune , and neurological illnesses. Some retroviruses, such as the lentiviruses and the spumaviruses, are capable of directly killing cells. Cytopathic (cell-killing) effects in infected T cells and cells in the brain may account for the profound immune deficiencies and neurological diseases induced by HIV and related lentiviruses.

Retroviruses are also capable of inducing latent infections, in which the virus is dormant, or persistent infections, in which low levels of the virus are continuously produced. These capabilities explain the life-long nature of retroviral infections, and render the diseases induced by these pathogens extremely difficult to treat.

Retroviruses and Cancer

Retroviruses are among several types of viruses that can induce cancer in the host organism. So-called slowly transforming viruses are exemplified by human T-lymphotropic virus (HTLV), which causes leukemia (a type of blood cancer) in humans. These viruses induce malignancy by a process called insertional mutagenesis. The initial event is thought to be retroviral integration near, and subsequent activation of, a cellular oncogene (c-onc ). Examples of c-onc include genes for growth factors, protein kinases , and transcription factors . Harold Varmus and Michael Bishop won the Nobel Prize for physiology or medicine in 1989 for their contributions to the discovery of oncogenes.

When a malignancy is triggered, tumors appear only after a long latent period of months or years, and these tumors are typically clonal in origin. That is, they arise by the rare transformation of a single cell. HTLV-1 is highly prevalent in people living in Japan, the Caribbean, and Africa, areas where approximately one percent of adults are infected. About one to three percent of infected individuals will eventually develop adult T-cell leukemia after an incubation period, which is usually several decades long. HTLV stimulates T-cell proliferation that could favor mutational events leading to cell transformation.

Acutely transforming retroviruses contain a viral oncogene (v-onc ) and induce polyclonal cancers (that is, many different cancer cells are derived in multiple transforming events) at high efficiency within a short time frame (weeks). The v-onc are derived by incorporation and modification (that is, by deletion of introns, mutations, and other such processes) of host-cell oncogenes. The v-onc are often expressed in great quantity, due to the highly active viral LTRs. Most acutely transforming retroviruses are replication-defective, because incorporation of the oncogene deletes an essential gene or genes. They therefore require a helper virus to propagate. An exception is Rous sarcoma virus, whose genome retains enough of the structural gene sequences to remain capable of replication.

see also DNA Libraries; Evolution of Genes; Gene Therapy; HIV; Oncogenes; Overlapping Genes; Reverse Transcriptase; RNA; RNA Polymerases; Virus.

Robert Garry

Bibliography

Varmus, Harold E. "Form and Function of Retroviral Proviruses." Science 216, no. 4548 (1982): 812-820.

Weinberg, Robert A. "How Cancer Arises." Scientific American 275, no. 3 (1996): 62-70.

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Retrovirus

Retrovirus

Retroviruses are a unique class of single-stranded ribonucleic acid (RNA) containing viruses, which replicate their genome through a double-stranded viral deoxyribonucleic acid (DNA) intermediate in the nucleus of the host cell. This is in contrast to all other RNA-containing viruses that replicate their genomes through double-stranded RNA intermediates almost always in the cytoplasm of host cells. Most retroviruses contain an RNA genome of 9 to 10 kilobases in length, which encodes a minimum of three genes required for replication. These are referred to as gag (structural proteins of the virus), pol (enzymes involved in replication), and env (envelope glycoproteins required for the virus to attach to a receptor of a new host cell). Human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), belongs to a subclass of retroviruses, the lentiviruses, which encode additional viral genes that permit the virus to grow in nondividing cells, such as white blood cells.

The remarkable replication pathway of retroviruses requires that once the virus enters the host cell, a viral pol geneencoded enzyme called reverse transcriptase (RT), which is packaged in virus particles, reverse transcribes the single-stranded RNA genome into a double-stranded DNA. This DNA intermediate migrates to the nucleus of the cell where it is integrated into the host cell genome. This process is catalyzed by another viral enzyme called integrase (IN). Since there is no matching sequence between the viral DNA and the host genomic DNA, sites of insertion are mostly randomly distributed. Because the viral DNA is now part of the cellular chromosome , it is duplicated whenever the cell's own DNA is replicated.

Transcription of the viral sequence from the integrated DNA to make messenger RNA (mRNA) requires cellular enzymes. Full-length viral mRNA is transported to the cytoplasm where it is either packaged into progeny virus or translated on non-membrane-bound (free) ribosomes to yield viral Gag and Gag-Pol polyproteins (assemblies of many similar proteins). These polyproteins in turn migrate to the cell membrane where they assemble into virus particles, containing RNA, which bud from the cell surface. Concomitantly, viral glycoproteins are translated as polyproteins from a smaller-sized, spliced viral mRNA on membrane-bound ribosomes. These polyproteins are processed in the endoplasmic reticulum , where they also go through an additional modification known as glycosylation, in which sugar groups are added to the protein. When virus particles bud from the cell, they pinch off a portion of the cell membrane, containing the viral glycoproteins. This membrane becomes an outer coating of the virus particle.

The Gag and Gag-Pol polyproteins are cleaved into the mature-sized proteins during or immediately after the budding process by a third viralencoded enzyme called protease (PR). Once the protein-cleaving proteolytic processing is complete, an infectious virus results, which can infect new cells.

During an active infection process, approximately 1 percent of a cell's resources are diverted to synthesis of virus genomes and proteins. Infected cells are therefore not killed. Most retroviruses activate expression of a cancer-causing gene, called an "oncogene," which transforms host cells so that they become immortalized, providing a long-term home for the retrovirus. Lentiviruses, including HIV, do not transform cells. Instead they cause cell death in some of the cell types in which they replicate. When these cells are important components of the immune system, an infected person loses the ability to mount an effective immune response, resulting in AIDS. This leaves the person susceptible to almost any opportunistic infection. Patients with HIV infection are treated with drugs that inhibit either RT or PR to slow the spread of virus. As of May 2001, the treatment of choice for HIV patients included two RT inhibitors and one PR inhibitor, and is known therefore as "triple therapy." These drugs do not cure AIDS because the viral genome is integrated into the host chromosome. Also, virus-containing drug-resistant enzymes can be rapidly selected in a treated patient, necessitating the need for multidrug clinical strategies. Thus the only sure defense against AIDS is not to become infected by the virus.

see also AIDS; Oncogenes and Cancer Cells; Protein Synthesis; Replication; Reverse Transcriptase; Transcription; Transposon; Virus

Jonathan Leis

Bibliography

Alberts, Bruce, et al. Molecular Biology of the Cell, 4th ed. New York: Garland Publishing, 2000.

Gallo, Robert. Virus Hunting: AIDS, Cancer, and the Human Retrovirus. Vancouver, WA: Vintage Books, 1991.

, and Gilbert Jay. The Human Retrovirus. San Diego, CA: Academic Press, 1991.

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retrovirus

retrovirus, type of RNA virus that, unlike other RNA viruses, reproduces by transcribing itself into DNA. An enzyme called reverse transcriptase allows a retrovirus's RNA to act as the template for this RNA-to-DNA transcription. The resultant DNA inserts itself into a cell's DNA and is reproduced along with the cell and its daughters. The life cycle is completed when the viral DNA in selected daughter cells makes an RNA copy of itself that covers itself in a protein coat and leaves the cell. Retroviruses sometimes destroy the cells whose DNA they alter, as with HIV, the virus that causes AIDS, and sometimes cause them to become cancerous, as with the viruses that cause certain leukemias. Lentiviruses are retroviruses that cause slowly progressing diseases, such as AIDS.

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Retrovirus

RETROVIRUS

Retroviruses replicate inside cells they have invaded, using an enzyme called "reverse transcriptase" to transcribe RNA into DNA. In this way they can evade the body's natural immune defense mechanisms as they make new copies of themselves. The most important retrovirus is the human immunodefeciency virus (HIV). HIV invades and destroys host cells, particularly T-helper lymphocytes, which are crucially important in maintaining the body's immune defense mechanisms. Disruption of immune defense mechanisms following the destruction of T-helper lymphocytes is the main way in which HIV leads to AIDS.

John M. Last

(see also: HIV/AIDS; Pathogenic Organisms )

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retrovirus

retrovirus An RNA-containing virus that converts its RNA into DNA by means of the enzyme reverse transcriptase; this enables it to become integrated into its host's DNA. Some retroviruses can cause cancer in animals: they contain oncogenes (cancer-causing genes), which are activated when the virus enters its host cell and starts to replicate. The special properties of retroviruses make them useful as vectors for inserting genetic material into eukaryotic cells. The best-known retrovirus is HIV, responsible for AIDS in humans. See also provirus.

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retrovirus

retrovirus Any of a large virus family (Retroviridae) that, unlike other living organisms, contain the genetic material RNA (ribonucleic acid) rather than the customary DNA (deoxyribonucleic acid). In order to multiply, retroviruses make use of a special enzyme to convert their RNA into DNA, which then becomes integrated with the DNA in the cells of their hosts. Diseases caused by retroviruses include acquired immune deficiency syndrome (AIDS).

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retrovirus

retrovirus A virus whose genetic material consists of RNA and which is able, by means of the enzyme reverse transcriptase, to manufacture its DNA equivalent and insert it into the genome of its host species. It has been suggested that this could be a way of overriding Weissmann's doctrine, and in effect causing Lamarckian inheritance. See neo-Lamarckism.

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retrovirus

retrovirus A virus whose genetic material consists of RNA and is able, by means of the enzyme reverse transcriptase, to manufacture its DNA equivalent and insert it into the genome of its host species. It has been suggested that this could be a way of overriding Weissmann's doctrine, and in effect causing Lamarckian inheritance. See NEO-LAMARCKISM.

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retrovirus

ret·ro·vi·rus / ˌretrōˈvīrəs; ˈretrōˌvīrəs/ • n. Biol. any of a group of RNA viruses that insert a DNA copy of their genome into the host cell in order to replicate, e.g., HIV.

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retrovirus

retrovirus (ret-roh-vy-rŭs) n. an RNA-containing virus that can convert its genetic material into DNA, which enables it to become integrated into the DNA of its host's cells. Retroviruses include HIV and viruses implicated in the development of some cancers.

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retrovirus

retrovirusArras, embarrass, harass •gynandrous, polyandrous •Pancras • charas • Tatras • disastrous •ferrous • leprous • ambidextrous •Carreras, mayoress •scabrous •cirrus, Pyrrhus •chivalrous •citrous, citrus •ludicrous • tenebrous •Cyrus, Epirus, papyrus, virus •fibrous • hydrous • Cyprus •retrovirus • monstrous •brachiosaurus, brontosaurus, canorous, chorus, Epidaurus, Horus, megalosaurus, pelorus, porous, sorus, stegosaurus, Taurus, thesaurus, torus, tyrannosaurus •walrus •ochrous (US ocherous) •cumbrous • wondrous • lustrous •Algeciras, Severus •desirous •Arcturus, Epicurus, Honduras •barbarous • tuberous • slumberous •Cerberus • rapturous •lecherous, treacherous •torturous • vulturous • Pandarus •slanderous • ponderous •malodorous, odorous •thunderous • murderous •carboniferous, coniferous, cruciferous, melliferous, odoriferous, pestiferous, somniferous, splendiferous, umbelliferous, vociferous •phosphorous, phosphorus •sulphurous (US sulfurous) •Anaxagoras, Pythagorasclangorous, languorous •rigorous, vigorous •dangerous • verdurous •cankerous, cantankerous, rancorous •decorous • Icarus • valorous •dolorous • idolatrous •amorous, clamorous, glamorous •timorous •humerus, humorous, numerous •murmurous • generous • sonorous •onerous • obstreperous • Hesperus •vaporous • viviparous • viperous •Bosporus, prosperous •stuporous • cancerous •Monoceros, rhinoceros •sorcerous • adventurous • Tartarus •nectarous • dexterous • traitorous •preposterous • slaughterous •boisterous, roisterous •uterus • adulterous • stertorous •cadaverous • feverous •carnivorous, herbivorous, insectivorous, omnivorous •Lazarus

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Retrovirus

Retrovirus

Resources

Retroviruses are viruses in which the genetic material consists of ribonucleic acid (RNA) instead of deoxyribonucleic acid (DNA). Retroviruses produce an enzyme known as reverse transcriptase that uses RNA as a template to manufacture DNA, which can then be permanently integrated into the DNA of the infected host cells.

Retroviruses have been known for a long time. In 1911, Peyton Rous (18791970) successfully isolated the agent that caused tumors in chickens. This agent, later called Rous sarcoma virus, was the first retrovirus to be discovered. In the 1960s, Howard Temin (19341994) proposed that retroviruses accomplished the replication of their genetic material by the aforementioned RNA-to-DNA route. This concept, which was called reverse transcription, garnered Temin and David Baltimore (1938) a Nobel Prize in medicine or physiology in 1975. The human T-cell leukemia virus (HTLV; now two types are known), the first diseases causing retrovirus of humans, was discovered in 1981, followed two years later by the discovery of HIV.

The known retroviruses are classified into three families: Retroviridae, Metaviridae, and Pseudoviridae. The HIV and HTLV types are members of the Retroviridae. Members of the family Metaviridae infect fungi and insects. Finally, members of the family Pseudoviridae infect yeast and insects. From the human perspective, the Retroviridae are the most immediate concern.

Many gene therapy treatments and experiments use disabled mouse retroviruses as a carrier (vector) to inject new genes into the host DNA. Retroviruses are rendered safe by adding, mutating, or deleting viral genes so that the virus cannot reproduce after acting as a vector for the intended delivery of new genes. Although viruses are not normally affected by antibiotics, genes can be added to retroviruses that make them susceptible to specific antibiotics.

As of 2006, researchers had discovered only a handful of retroviruses that infect humans. Human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS), is a retrovirus. Another human retrovirus, human T-cell leukemia virus (HTLV), was discovered three years prior to the discovery of HIV. Both HTLV and HIV attack human immune cells called T cells. T cells are the linchpin of the human immune response. When T cells are infected by these retroviruses, the immune system is disabled and several serious illnesses result. HTLV causes a fatal form of cancer called adult T cell leukemia. HTLV infection of T cells changes the way the T cells work in the body, causing cancer. HIV infection of T cells, however, eventually kills T cells, rendering the immune system powerless to stave off infections from microorganisms.

Retroviruses are sphere-shaped viruses that contain a single strand or a couple of strands of RNA. The sphere-shaped capsule of the virus consists of various proteins. The capsule is studded on the outside with proteins called receptor proteins. In HIV, these receptor proteins bind to special proteins on T cells called CD4 receptors. CD4 stands for cluster of differentiation, and CD type 4 is found on specific T cells called helper cells. The human retroviruses discovered so far bind only to CD4 receptors, which makes their affinity for T helper cells highly specific.

The retrovirus receptor docks with a CD4 receptor on a T cell, and enters the T cell through the T cell membrane. Once inside, the retrovirus begins to replicate. But because the retroviruss genetic material consists of RNA, not DNA, replication is more complicated in a retrovirus than it is for a virus that contains DNA.

In all living things, DNA is the template by which RNA is transcribed. DNA is a double-stranded molecule that is located within the nucleus of cells. Within the nucleus, DNA transcribes RNA, a single-stranded nucleic acid. The RNA leaves the nucleus through tiny pores and enters the cytoplasm, where it directs the synthesis of proteins. This process has been called the central dogma of genetic transcription. No life form has been found that violates this central dogma except retroviruses. In retroviruses, the RNA is used to transcribe DNA, which is exactly opposite to the way genetic material is transcribed in all other living things. This reversal is why they are named retrograde, or backwards, viruses.

In addition to RNA, retroviruses contain an enzyme called reverse transcriptase. This is the enzyme that allows the retrovirus to make a DNA copy from RNA. Once this DNA copy is made, the DNA inserts itself into the T cells DNA. The inserted DNA then begins to produce large numbers of viral RNA that are identical to the infecting viruss RNA. This new RNA is then transcribed into the proteins that make up the infecting retrovirus. In effect, the T cell is transformed into a factory that produces more retroviruses. Because reverse transcriptase enzyme is unique to retroviruses, drugs that inhibit the action of this enzyme are used to treat retroviral infection, such as HIV. Reverse transcriptase is vital for retrovirus replication, but not for human cell replication. Therefore, modern reverse transcriptase inhibitor drugs are specific for retroviruses. Often, reverse transcriptase inhibitors are used in combination with other drugs to treat HIV infection.

Retroviruses are especially lethal to humans because they cause a permanent change in the T cells DNA. Other viruses merely commandeer their host cells cytoplasm and chemical resources to make more viruses; unlike retroviruses, they do not insert their DNA into the host cells DNA. Nor do most viruses attack the bodys T cells. Most peoples cells, therefore, can recover from an attack from a virus. Eventually, the bodys immune system discovers the infection and neutralizes the viruses that have been produced. Any cells that contain viruses are not permanently changed by the viral infection. Because retroviruses effect a permanent change within important cells of the immune system, cellular recovery from a retrovirus infection does not occur.

In 1980, researchers headed by Robert Gallo at the National Cancer Institute discovered the first human retrovirus. They found the virus within leukemic T cells of patients with an aggressive form of T-cell cancer. These patients were from the southern United States, Japan, and the Caribbean. Almost all patients with this form of cancer were found to have antibodies (immune system proteins made in response to an infection) to HTLV.

HIV is perhaps the most famous retrovirus. Discovered independently by several researchers in 1983, HIV is now known to be the causative agent of AIDS. People with AIDS test positive for HIV antibodies, and the virus itself has been isolated from people with the disease.

HIV attacks T cells by docking with the CD4 receptor on its surface. Once inside the cell, HIV begins to transcribe its RNA into DNA, and the DNA is inserted into the T cells DNA. However, new HIV is not released from the T cell right away. Instead, the virus stays latent within the cell, sometimes for 10 years or more. For reasons that are not yet clear, at some point the virus again becomes active within the T-cell, and HIV particles are made within the cell. The new HIV particles bud out from the cell membrane and attack other T cells. Soon, all of the T cells of the body are infected and die. This infection cycle explains why very few virus particles are found in people with the HIV infection (those who do not yet have AIDS); many particles are found in people who have fulminate AIDS.

No cure has yet been found for AIDS. Researchers are still unsure about many aspects of HIV infection, and research into the immune system is still a relatively new science. Several anti-retroviral drugs, such as AZT, ddI, and ddC, have been administered to people with HIV. These drugs do not cure HIV infection; but they usually postpone the development of AIDS. AIDS is almost invariably fatal.

KEY TERMS

Adult T-cell leukemia (ATL) A form of cancer caused by the retrovirus HTLV.

Antibody A molecule created by the immune system in response to the presence of an antigen (a foreign substance or particle). It marks foreign microorganisms in the body for destruction by other immune cells.

Seropositive Describes the condition in which ones blood tests positive for an antibody against a specific microorganism.

T cells Immune-system white blood cells that enable antibody production, suppress antibody production, or kill other cells.

Transcription The process of synthesizing RNA from DNA.

Simian immunodeficiency virus (SIV) is the primate version of HIV. In fact, monkeys infected with SIV are used to test AIDS drugs for humans. Rous sarcoma virus (RSV) causes cancer in chickens and was the first retrovirus identified. Feline leukemia virus (FELV) causes feline leukemia in cats and is characterized by symptoms similar to AIDS. Feline leukemia is a serious disease that, like AIDS, is fatal. Unlike AIDS, a vaccine has been developed to prevent this disease.

See also Autoimmune disorders; DNA replication.

Resources

BOOKS

Bartlett, John G. and Ann K. Finkbeiner. The Guide to Living with HIV Infection. Baltimore: The Johns Hopkins University Press, 2006.

Grodeck, Brett and Daniel S. Berger. The First Year-HIV: An Essential Guide for the Newly Diagnosed. Washington, DC: Marlowe & Company, 2003.

Karim, Salim and Quarraisha Karim. HIV/AIDS in South Africa. Cambridge: Cambridge University Press, 2006.

PERIODICALS

Brooks, J.I., E.W. Rud, R.G. Pilon, et al. Cross-Species

Retroviral Transmission from Macaques to Human Beings. Lancet 360 (August 2002): 387388.

Gallo, R.C., A.S. Liski, and F. Wong-Staal. Origin of the T cell Leukemia-Lymphoma Virus. Lancet (ii) (1983): 962963.

Brian Hoyle

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Retrovirus

Retrovirus

Retroviruses are spherical viruses that contain ribonucleic acid (RNA) as their genetic material. In contrast, most other organisms, including humans, store their genetic information in the form of deoxyribonucleic acid (DNA) . Retroviruses are of concern to humans because of their disease causing ability. Examples of retroviruses include human T cell leukemia virus, which causes cancer in humans, and the several types of human immunodeficiency virus (HIV), which is widely acknowledged to be the cause of acquired immunodeficiency syndrome (AIDS ).

In 1911, Peyton Rous successfully isolated the agent that caused tumors in chickens. This agent, later called Rous sarcoma virus, was the first retrovirus to be discovered. In the 1960, Howard Temin proposed that retroviruses accomplished the replication of their genetic material by going from RNA through DNA to RNA. This concept, which was called reverse transcription, garnered Temin and David Baltimore a Nobel Prize in medicine or physiology in 1975. The human T cell leukemia virus (HTLV; now two types are known), the first diseases causing retrovirus of humans, was discovered in 1981, followed two years later by the discovery of HIV.

The known retroviruses are classified into three families: Retroviridae, Metaviridae, and Pseudoviridae. The HIV and HTLV types are members of the Retroviridae. Members of the family Metaviridae infect fungi and insects . Finally, members of the family Pseudoviridae infect yeast and insects. From the human perspective, the Retroviridae are the most immediate concern.

Retroviruses produce new virus particles inside of host cells that they have infected. The infection process begins when the virus binds to a specific molecule (called a receptor) on the surface of the host cell. The host receptor has not been produced to specifically encourage the binding of retroviruses. Rather, the retroviruses evolved to exploit the surface molecule as a target.

Once inside the host cell, the viral RNA is freed from the viral particle, and is reverse transcribed into DNA. The viral DNA can then become part of the host's DNA, in a process called integration. When the host's DNA is used to make new RNA, the viral DNA produces new viral RNA. The RNA can become packaged in new viral particles, which are released from the cell (a process called budding). The replication cycle can be repeated over and over again with other host cells.

Some of the host cells that can be targeted include cells that are important for the functioning of the immune system . With these cells not operating properly, the host is at risk for infections. Indeed, many AIDS patients die from infections and maladies like cancer than from the HIV infection.

As of 2002, no cure exists for the leukemia caused by HTLV or for AIDS (the cause of HIV.) Several candidate HIV vaccines have not so far provided adequate protection.

Prevention is the only way to avoid these retroviral diseases. Because the retroviruses responsible may be transmitted during sexual contact, using condoms and avoiding unsafe sexual practices in which blood , semen, or vaginal fluids are exchanged has been shown to be highly effective in preventing retrovirus transmission. Avoiding the injection of drugs or the sharing of needles is another way to prevent transmission.

During the 1970s, the blood collected in Canada and the United States was subject to viral contamination, even with HIV. However, stringent control practices have once again made the blood supplies generally safe. HTLV is not as large a threat in the United States as it is in other areas of the world that are endemic for the virus. Estimates are that HTLV-infected blood donors constitute about 0.025% of all U.S. blood donors.

See also Autoimmune disorders; DNA replication.


Resources

books

Coffin, J.M., S.H. Hughes, and H.E. Varmus. Retroviruses. Cold Spring Harbor, NY: Cold Spring Harbor Press, 1997.


periodicals

Brooks, J.I., E.W. Rud, R.G. Pilon, et al. "Cross-Species Retroviral Transmission from Macaques to Human Beings." Lancet 360 (August 2002): 387–388.

Gallo, R.C., A.S. Liski, and F. Wong-Staal. "Origin of the T cell Leukemia-Lymphoma Virus." Lancet (ii) (1983): 962–963.

Weiss, R., "Getting to Know HIV." Tropical Medicine and International Health. 5 (July 2000): A10–15.

Zhang, Z-Q., T. Schuler, M. Zupancic, et al. "Sexual Transmission and Propogation of SIV and HIV in Resting and Activated CD4+ T Cells." Science 286 (November 1999): 1353–1357.


Brian Hoyle

KEY TERMS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Adult T cell leukemia (ATL)

—A form of cancer caused by the retrovirus HTLV.

Antibody

—A molecule created by the immune system in response to the presence of an antigen (a foreign substance or particle). It marks foreign microorganisms in the body for destruction by other immune cells.

Seropositive

—Describes the condition in which one's blood tests "positive" for an antibody against a specific microorganism.

T cells

—Immune-system white blood cells that enable antibody production, suppress antibody production, or kill other cells.

Transcription

—The process of synthesizing RNA from DNA.

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