Retroviruses are viruses in which the genetic material consists of ribonucleic acid (RNA ) instead of the usual deoxyribonucleic acid (DNA ). Retroviruses produce an enzyme known as reverse transcriptase that can transform RNA into DNA, which can then be permanently integrated into the DNA of the infected host cells.
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 2002, researchers have 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 retrovirus's 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 cell's DNA. The inserted DNA then begins to produce large numbers of viral RNA that are identical to the infecting virus's 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 cell's DNA. Other viruses merely commandeer their host cell's cytoplasm and chemical resources to make more viruses; unlike retroviruses, they do not insert their DNA into the host cell's DNA. Nor do most viruses attack the body's T cells. Most people's cells, therefore, can recover from an attack from a virus. Eventually, the body's 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 affect 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 cell's 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 AIDS. These drugs do not cure HIV infection; but they usually postpone the development of AIDS. AIDS is almost invariably fatal.
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 AIDS, recent advances in research and treatment; Immunogenetics; T cells or T lymphocytes; Viral genetics; Viral vectors in gene therapy; Virus replication; Viruses and responses to viral infection
"Retroviruses." World of Microbiology and Immunology. . Encyclopedia.com. (April 29, 2017). http://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/retroviruses
"Retroviruses." World of Microbiology and Immunology. . Retrieved April 29, 2017 from Encyclopedia.com: http://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/retroviruses
Seroconversion is a term that refers to the development in the blood of antibodies to an infectious organism or agent. Typically, seroconversion is associated with infections caused by bacteria , viruses , and protozoans. But seroconversion also occurs after the deliberate inoculation with an antigen in the process of vaccination . In the case of infections, the development of detectable levels of antibodies can occur quickly, in the case of an active infection, or can be prolonged, in the case of a latent infection. Seroconversion typically heralds the development of the symptoms of the particular infection.
The phenomenon of seroconversion can be important in diagnosing infections that are caused by latent viruses. Examples of viruses include hepatitis B and C viruses, the Epstein Barr virus, and the Human Immunodeficiency Virus (HIV ). When these viruses first infect people, the viral nucleic acid can become incorporated into the genome of the host. As a result, there will not be an immune response mounted against the virus. However, once viral replication has commenced antibodies to viral proteins can accumulate to detectable levels in the serum.
Seroconversion is am important aspect of Acquired Immunodeficiency Syndrome (AIDS ). Antibodies to HIV can sometimes be detected shortly after infection with the virus, and before the virus becomes latent. Symptoms of infection at this stage are similar to the flu, and disappear quickly, so treatment is often not sought. If, however, diagnosis is made at this stage, based on presence of HIV antibodies, then treatment can begin immediately. This can be important to the future outlook of the patient, because often at this stage of the infection the immune system is relatively undamaged. If seroconversion occurs following activation of the latent virus, then immune destruction may already be advanced.
The presence of antibodies in the serum occurs much earlier in the case of infections that occur very soon after the introduction of the infectious microorganism. The type of antibody present can be used in the diagnosis of the infection. Additionally, seroconversion in the presence of symptoms but in the absence of detectable microorganisms (particularly bacteria) can be a hallmark of a chronic infection caused by the adherent bacterial populations known as biofilms. Again, the nature of the antibodies can help alert a physician to the presence of a hitherto undetected bacterial infection , and treatment can be started.
See also Antibiotic resistance, tests for; Antibody and antigen; Antibody-antigen, biochemical and molecular reactions; Antibody formation and kinetics; Immunity, active, passive and delayed; Immunochemistry; Immunodeficiency disease syndromes; Serology
"Seroconversion." World of Microbiology and Immunology. . Encyclopedia.com. (April 29, 2017). http://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/seroconversion
"Seroconversion." World of Microbiology and Immunology. . Retrieved April 29, 2017 from Encyclopedia.com: http://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/seroconversion