HIV
HIV (Human Immunodeficiency Virus) is a retrovirus that infects cells of the human immune system. It is widely accepted that infection with HIV causes AIDS (Acquired Immunodeficiency Syndrome), a disease characterized by the destruction of the immune system. In the United States and Europe, antibodies to HIV are one of the criteria for a diagnosis of AIDS.
HistoryHIV has been used since 1986 as the name for the retrovirus that was first proposed as the cause of AIDS by Luc Montagnier of France (who initially named it LAV, Lymphadenopathy-Associated Virus) and by Robert Gallo of the United States (who initially named it HTLV-III, Human T Lymphotropic Virus type III).UNAIDS estimated that at the end of 2004 there were between 36 and 44 million people around the world living with HIV, of whom 25 million were in sub-Saharan Africa. Global estimates for new HIV infection in 2004 were 4.3-6.4 million. (AIDS epidemic update December 2004). Transmission of HIVHIV is transmitted through penetrative (anal or vaginal) and oral sex, blood transfusion, the sharing of contaminated needles in health care settings and through drug injection, and between mother and infant during pregnancy, childbirth and breastfeeding according to a leading international health care source UN AIDS in UNAIDS transmission. The use of physical barriers such as the latex condom is widely advocated to reduce the risk of sexual transmission of HIV.The WHO estimated in 2000 that 25% of the units of blood transfused in Africa were not tested for HIV and 5% to 10% of cases of HIV infection in Africa were transmitted via blood. [1] Signs and symptomsThe development of antibodies to HIV usually takes place between 6 weeks and 3 months after an infection has occurred. Most people infected with HIV do not know that they have become infected, because no symptoms develop immediately after the initial infection. During the weeks between HIV infection and the development of antibodies to HIV, a person may be highly infectious. Some people have a glandular fever-like illness (with fever, rash, joint pains and enlarged lymph nodes), in the days following HIV infection (Kahn & Walker 1998). HIV infectionPeople who become infected with HIV may have no symptoms for up to 10 years, but they can still transmit the infection to others. Acute HIV infection progresses over time to asymptomatic HIV infection and then to early symptomatic HIV infection and later, to AIDS, which is identified on the basis of certain infections, grouped by the World Health Organization. Most of these conditions are opportunistic infections that can be easily treated in healthy people. Most individuals infected with HIV will progress to AIDS if not treated. However, there is a tiny subset of patients who develop AIDS very slowly, or never at all. These patients are called non-progressors.
WHO recommends that HIV infected adolescents and adults with these infections and/or a T cell count of 200 per mm3 start antiretroviral therapy. (UNAIDS 2005) TreatmentHIV infection is a chronic medical condition that can be treated, but not yet cured. There are effective means of preventing complications and delaying, but not preventing, progression to AIDS. At the present time, not all persons infected with HIV have progressed to AIDS, but it is generally believed that the majority will. People with HIV infection need to receive education about the disease and treatment so that they can be active partners in decision making with their health care provider.A combination of several antiretroviral agents, termed Highly Active Anti-Retroviral Therapy HAART, has been highly effective in reducing the number of HIV particles in the blood stream (as measured by a blood test called the viral load). This can improve T-cell counts. This is not a cure for HIV, and people on HAART with suppressed levels of HIV can still transmit the virus to others through sex or sharing of needles. There is good evidence that if the levels of HIV remain suppressed and the CD4 count remains greater than 200, then life and quality of life can be significantly prolonged and improved. Treatment guidelines are changing constantly. The current guidelines for antiretroviral therapy [1] from the World Health Organization reflect the 2004 changes to the guidleines to defer retroviral treatment in patients with no symptoms who have more than 350 T-cells and viral load under 100,000. There are several concerns about antiretroviral regimens. The drugs can have serious side effects. Regimens can be complicated, requiring patients to take several pills at various times during the day. If patients miss doses, drug resistance can develop. [1] In 2004, a possible vaccine was found. In order for the vaccine to work, the patient must first be diagnosed with the virus. Once the patient is treated, T-cell counts have been found to stop dropping. [1] In 2005, the Centers for Disease Control and Prevention in the United States recommended a 28-day HIV drug regimen for those who believe they may have had contact with the virus. The drugs have demonstrated effectiveness in preventing the virus nearly 100% of the time in those who received treatment within the initial 24 hours of exposure. The effectiveness falls to 52% of the time in those who are treated within 72 hours; those not treated within the first 72 hours are not recommended candidates for the regimen. Life cycle of HIVHIV enters a CD4+ helper T-cell by bonding with either CXCR4 or both CXCR4 and CCR5 depending on what stage the HIV infection is in. A cofactor protein (fusin) is required to assist binding of the viron to the membrane of the T-cell. During the early phases of an HIV infection typically both CCR5 and CXCR4 are bound while late stage infection often involve HIV mutations that only bind to CXCR4. Once HIV has bound to the CD4+ T-cell a viral protein known as GP41 penetrates the cell membrane and the HIV RNA and various enzymes including but not limited to reverse transcriptase, integrase and protease are injected into the cell. The host T-cell can process RNA into proteins (as in Polio virus) but this doesn't happen with HIV. Instead, HIV is stabilised by copying it into DNA and inserting it into the host cell's chromosomes. This means the virus can perform more subtle functions by using the host transcription machinery. The virus generates DNA from the HIV RNA using the reverse transcriptase enzyme to perform reverse transcription. This process can be inhibited by drugs. If this succeeds the pro-viral DNA must then be integrated into the host cell DNA using the integrase enzyme. If the pro-viral DNA becomes integrated into the host cell's DNA the cell is now fully infected but not actively producing HIV proteins. This is the latent stage of an HIV infection during which the infected cell can be an "unexploded bomb" for potentially a long time. To actively produce virus, certain transcription factors need to be present in the cell. The most important is called NF-kB (NF Kappa B) and is present once the T cells becomes activated. This means that those cells most likely to be killed by HIV are in fact those currently fighting infection. The production of the virus is regulated, like that of many viruses. Initially the integrated provirus is copied to mRNA which is then spliced into smaller chunks. These small chunks produce the regulatory proteins Tat (which encourages new virus production) and Rev. As Rev accumulates it gradually starts to inhibit mRNA splicing. At this stage the structural proteins Gag and Env are produced from the full-length mRNA. Additionally the full-length RNA is actually the virus genome, so it binds to the Gag protein and is packaged into new virus particles. Interestingly HIV-1 and HIV-2 appear to package their RNA differently - HIV-1 will bind to any appropriate RNA whereas HIV-2 will preferentially bind to the mRNA which was used to create the Gag protein! This may mean that HIV-1 is better able to mutate (HIV-1 causes AIDS faster than HIV-2 and is the majority species of the virus). The virus starts to form under the cell membrane, in special cholesterol-rich regions, and gradually buds outside. Once outside it has to undergo a maturation step or else it isn't infectious. The virus protease enzyme cleaves Gag into several smaller proteins (Matrix, Capsid, p2, Nucleocapsid, p1 and P6) and this step can be inhibited by drugs. The virus is then able to infect a further cell. Structure of the virusHIV looks quite different to the classic retroviruses described in the 1960s. It is around 120nm in diameter (120 billionths of a meter - a red blood cell is around 60 times larger at 7 millionths of a meter) and roughly spherical. There are two forms of the virus. They both consist of a lipid envelope surrounding a protein/RNA core.Immature form: When the virus leaves the cell it is not infectious and the inner part of the virus particle contains a spherical core (stains dark on electron micrographs). There are also spikes on the outer membrane that are the Env proteins (gp120 and gp41). Sometimes a virus can be seen during the process of budding, when it looks like a dark arc sitting under the cell membrane - this observation meant that HIV was originally classed as a type C retrovirus. The Env proteins link together in groups of three (trimers).
Mature form: Once the virus protease has cleaved the Gag proteins, the core rearranges into a truncated cone (imagine a traffic cone sliced at an angle across the top!) Some reports also show a small filament linking the core to the membrane. The envelope spikes are often much rarer on mature particles since they are easily dislodged. It is the mature conical core that makes HIV so easily identifiable. Inside the virus there are two identical strands of RNA, in the same way that we have two identical copies of each chromosome. The RNA is coated by the CA protein (formed from Gag) and is not easily seen unless the virus particles are broken apart. The reverse transcriptase enzyme, which includes integrase, is also packaged into the virus along with certain other important proteins (some from the virus, some captured from the cell) and a tRNA molecule that initiates the reverse transcription process. Because the virus contains certain proteins it needs to replicate, injection of the pure RNA will not result in a successful infection. HIV has several major genes coding for structural proteins that are found in all retroviruses, and several non-structural or "accessory" genes that are unique to HIV. General retrovirus genes
Specific HIV genes
References
See also
External links
Websites for HIV
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