HIV

From MicrobeWiki, the student-edited microbiology resource
Jump to: navigation, search
This student page has not been curated.

A Microbial Biorealm page on the genus HIV

Classification

Virus; Retro-transcribing viruses; Retroviridae; Orthoretrovirinae; Retroviridae; Lentivirus; Human Immunodeficiency Virus (3)

Description and significance

In the United States, Human Immunodeficiency Virus (HIV) disease was first discovered in 1981 in San Francisco and New York City. Human immunodeficiency virus is a member of the retrovirus. If not treated early it can cause acquired immunodeficiency syndrome (1). Retroviruses like HIV, store their genetic material on long strands of RNA. (2). HIV is found within humans and the disease is spread by damaging and destroying humans’ blood cells, called CD4+ T cells (2). Currently, there is no drug that can completely cure HIV infection and also no vaccine to prevent from future infection. There are few antiretroviral drugs that can slow the disease progression by inhibiting the function of proteins involved at different stages of the HIV life-cycle (1). However, after span of time HIV become resistant to these drugs due to high rate of genetic mutation. Most drugs that target the virus also damage the host. Drugs that can inhibit enzymes specific to the virus are, therefore, less likely to cause side effects in the host. Moreover, even highly active antiretroviral therapy like HAART (a combination of three-four antiretroviral drugs) cannot destroy the virus because they reservoir in the host genome (1). There are two types of HIV, HIV-1 and HIV-2, both still damages the immune system of humans. Many scientists believe that a type of chimpanzee in West Africa was a source of HIV infection in humans because of their version of immunodeficiency virus called simian immunodeficiency virus (5). They believed the virus was transmitted to humans when hunting infected chimpanzees and mutated into HIV. Over decades, the virus slowly spread across Africa and later into other parts of the world. In 1987, HIV-2 was isolated from AIDS patients in West Africa. HIV-2 transmits and leads to AIDS like HIV-1. However, a person affected with HIV-2 individuals are less infectious but as that disease advances infectiousness increases. HIV-2 infections are predominantly found in West Africa (5). Since the first discovery of AIDS in 1981, work has been done to prevent and care for the infection of HIV. With the amount of research there are still many questions about HIV and AIDS.

Genome structure

The HIV virus is diploid and contains two plus-stranded RNA copies of its genome(nise).HIV genome has 9,749 nucleotides and the RNA genome encodes at least 9 proteins, Gag, Pol, Env, Tat, Rev, Nef, Vif, Vpu and Vpr. Three of the HIV genes; Gag, Pol and Env contain information needed to make structural proteins for new virus particles. The other six genes, Tat, Rev, Nef, Vif, Vpr and Vpu, code for proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease (4).

Cell structure, metabolism & life cycle

Unlike most bacteria, HIV particles are too small to be seen through an ordinary microscope but can be seen clearly with an electron microscope. HIV is an enveloped RNA virus. Outside of a human cell; HIV exists as roughly spherical particles (virions). The surface of each particle is studded with lots of little spikes. HIV particles surround themselves with a coat of fatty material known as the viral envelope. Projecting from this are around 72 little spikes, which are formed from the proteins gp120 and gp41. Below the viral envelope is a layer called the matrix, which is made from the protein p17 (7). The proteins gp120 and gp41 together make up the spikes that project from HIV particles, while p17 forms the matrix and p24 forms the core(7). The viral core is usually rod-shaped and is made from the protein p24. Inside the core is three enzymes required life cycle for HIV replication is reverse transcriptase, integrase and protease. Also held within the core is HIV's genetic material, which consists of two identical strands of RNA (7). In order for HIV to replicate itself it must infect cells of living organisms. Virus replication: 1) Membranes of the virus and the host cell fuse, and viral RNA and reverse transcriptase enter the host's cytoplasm. 2) Reverse transcriptase allows viral RNA to be copied to DNA. 3) Viral DNA is incorporated into the host chromosome as provirus. 4) Transcription and translation of viral proteins: viral RNA becomes incorporated into viral particles and is transcribed. 5) Viral particles bud out of the host cell, acquiring an envelope in the process (6).

Ecology (including pathogenesis)

Like all viruses, HIV cannot grow or reproduce on its own. In order to make new copies of itself it must infect the cells of a living organism. HIV is found in humans, but it was believed to be originally found in West-Central African Chimpanzees. Many scientists believed that HIV was exposed to humans when hunters killed chimpanzee through hunting. It was also claimed that homosexual contact is another source of HIV within the United States, although heterosexual transmission is the most frequent spread of HIV (2). HIV is transmitted in three ways: by sexual contact, by blood (through transfusion, blood products, or contaminated needles), or by passage from mother to child. It cannot be spread outside the body such as though sweat or shaking hands. Within a few weeks of being infected with HIV, some people develop flu-like symptoms while others have no symptoms at all. People living with HIV may appear and feel healthy for several years; however, even if they feel healthy, HIV is still affecting their bodies. Many people with HIV, including those who feel healthy, can benefit greatly from current medications used to treat HIV infection. These medications can limit or slow down the destruction of the immune system, improve the health of people living with HIV, and may reduce their ability to transmit HIV. Untreated early HIV infection is also associated with many diseases including cardiovascular disease, kidney disease, liver disease, and cancer. AIDS is the late stage of HIV infection, when a person’s immune system is severely damaged and has difficulty fighting diseases and certain cancers. Before the development of certain medications, people with HIV could progress to AIDS in just a few years. Currently, people can live longer with HIV before they develop AIDS (1).

Interesting feature

Despite repeated exposure, some individuals never become infected with HIV. These individuals often have unusual helper T cells with a less-efficient variant of the co-receptor CCR5, which is necessary for viral entry into helper T cells (1). There are also individuals who become infected, but do not progress to AIDS. These long-term survivors, or long-term non-progressors, include individuals who have been AIDS-free as long as eighteen years after infection (1). A variety of factors may be responsible; for example, infection with less-virulent viruses. Some long-term non-progressors seem to have CD8 cells, which are particularly adept at curtailing HIV infection (1). Several investigators, including Jay Levy (University of California, San Francisco), are evaluating the CD8 cells of long-term survivors to see if they secrete an antiviral protein or proteins that may act against HIV (1). Scientists have taken a number of approaches to the development of a vaccine for HIV, but the nature of the virus presents significant challenges. HIV infects only humans and chimpanzees. Evaluating vaccine effectiveness in the chimpanzee model is problematic for several reasons. Chimpanzees are scarce, expensive, and do not show signs of disease when infected. There are also ethical concerns raised because chimpanzees are our closest evolutionary relatives. An alternative is the development of a monkey model using simian immunodeficiency virus (SIV) that has been genetically engineered to express HIV components (1). The problem with this approach is what will happen when a vaccine that was developed using monkey models is administered to humans.

References

1.HIV and AIDS. Retrieved from http://www.learner.org/courses/biology/textbook/hiv/hiv_8.html Oct/`23/2011

2.HIV. Retrieved from www. CDC.org. Oct/24/11

3.HIV. Retrieved from http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=12721 Oct. 24/11

4.Hunt, Richard, (2010) Human Immunodeficiency Virus and AIDS Structure: The Genome and Proteins of HIV. Microbiology and Immunology Online. University of South Carolina of Medicine. Retrieved from http://pathmicro.med.sc.edu/lecture/hiv9.htm. Oct/25/11

5.Kanki, P., Hamel,, D., Sankalé, J., Hsieh, C., Thior, I., Barin, F., Woodcock, S., & Ndiaye, A. (1998). Human immunodeficiency virus type 1 subtypes differ in disease progression. Journal of Infectious Diseases, 179 (1), 68-73.

6.Nielsen, M., Pedersen, F., & Kjems, J. (2005). Molecular strategies to inhibit hiv-1 replication. BioMed Central Page 1 of 20 Retrovirology, 2(10), 1-20.

7.Tyagi, A., Ahmed, F., Thakur, N., Sharma, A., Raghava, G., & Kumar, M. (2011). Hivsirdb: A database of HIV inhibiting sirnas. Bioinformatics Centre, Institute of Microbial Technology, 6(10), 1-6.