Overview

The Human Immunodeficiency Virus (abbreviated to HIV) is the virus that is responsible for AIDS*. HIV is a retrovirus. A retrovirus is a virus which has an enzyme called reverse transcriptase, which it uses to transcribe viral RNA into provirus DNA which is integrated into the host-cell genome. (The virus' genome is written in RNA, and the human genome is DNA, so it copies the RNA into DNA and inserts it into the human host cell's DNA).

There are two types of HIV: HIV-1 and HIV-2. Most people in the world who carry the HIV virus have HIV-1. HIV-2 is mostly found among people in West Africa. The genetic sequences of HIV-1 and HIV-2 are only partially homologous. They are both related to SIVs (Simian Immunodeficiency Viruses), and may have originated from them. It seems HIV-1 is closer to a strain of SIV which infects chimpanzees, while HIV-2 is similar to a strain of SIV which infects the sooty mangabey monkey, which is found in West Africa.

When speaking of HIV in this node, I will be referring mostly to HIV-1, as it is the strain which is responsible for the epidemic in most of the world. It should be mentioned that HIV-2, will not necessarily be detected by laboratory tests for HIV-1.

HIV Structure

The mature HIV virion (a virion is a mature virus capable of surviving in an extracellular environment) is a roughly spherical (actually icosahedral) particle with a diameter of ~100 nanometers.



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The labels, clockwise, from top left: RNA, enzymes,  capsid, viral envelope, viral proteins


The HIV genome is a 9-kilobase single-stranded RNA. It contains the three genes common to retroviruses: gag, env and pol, and at least six additional genes. Aside from the RNA, the enzymes reverse transcriptase, protease, ribonuclease and integrase are also present. The outer surface has 72 spikes formed by the two major viral-envelope glycoproteins (gp120 and gp41). gp120 aids in the binding of the virus to the target cells with CD4 receptors.

HIV Infection

The main target cells for HIV infection are human CD4 T-lymphocytes and macrophages. The CD4 glycoprotein on the surface of these cells serves as a receptor for HIV. The gp120 on the virion binds to the CD4 receptor on the host cell. It has recently been discovered that coreceptors (either CCR5 or CXCR4) for HIV-1 must also be present on the target cells for the virion to enter. Cells without these coreceptors may avoid infection by HIV.

Once it has entered the cell, the virus uncoats from the envelope and releases its RNA. Reverse transcriptase transcribes the viral RNA to proviral DNA. This proviral DNA which is then inserted into host cell genomic DNA by the integrase enzyme. What this means, simply, is that the enzyme, reverse transcriptase, makes a copy of the viral RNA so that it is coded in human DNA. Then this is inserted into the DNA strand. So part of the cell's DNA now codes for the virus. Once the HIV proviral DNA is within the infected cell's genome, it cannot be eliminated or destroyed except by destroying the cell itself.

There are two states that an infected cell can be in: latent or active. When the cell is latent, no transcription of DNA to viral RNA occurs, but the virus may spread by cell division (basically, the entire DNA of the cell copies itself and is incorporated into a new cell, with it the viral DNA). Most of the cellular infection is in fact latent. If the infected cell is activated, transcription of the viral DNA begins, resulting in the production of multiple copies of viral RNA. This RNA codes for the production of the viral proteins and enzymes. Then, RNA is translated to a polypeptide sequence. Viral protease (an enzyme which cuts polypeptides) cuts the long chain into its individual enzyme components (such as reverse transcriptase), which then facilitate the production of new viruses. Then, the viral core containing HIV RNA, core proteins and enzymes, moves to the cell surface, acquires gp120 and gp41, and buds through the plasma membrane, to be released as infectious virus.

Reverse transcriptase is very prone to error. This means that is makes a lot of mistakes when copying viral RNA to proviral DNA. Thus, the rate of HIV mutation is very high, which makes a large genotypic and phenotypic diversity (many differences both in the genome and in the expression of the genome - the enzymes, the outer coat, etc.) This complicates matters when attempting to treat AIDS, as the viruses are so different, and it is hare to find things that are common to all of them, so that they can be vanquished.

For example, inhibitors of this viral protease can be used to fight HIV infection, by blocking the ability of the protease to cleave the viral polypeptide into functional enzymes. But the many mutations mean that the viral protease can mutate, and a drug which manages to inhibit one version of this protease may not work on another.

This is the reason that treatment for HIV focuses on multiple-drug therapies. when many parts of the virus are attacked, it is less likely that mutation will have changed all of them.

The Immune System

After initial entry of HIV, replication may at first occur in cells around the infection point, but the virus quickly moves to the lymphoid tissues of the body, (mainly in lymph nodes, the spleen, liver, gut and bone marrow).

The primary target of HIV is the immune system itself, and the main targets are CD4 lymphocytes. HIV infection may appear latent for years. In this period, there is ongoing immune system destruction, but enough of the immune system remains intact to prevent most infections. Eventually, when a significant number of CD4 lymphocytes have been destroyed and when production of new CD4 cells cannot match destruction, then failure of the immune system leads to the appearance of clinical AIDS. The precise method of CD4 lymphocyte destruction is not certain.

Progression of HIV Infection

About 3-6 weeks after infection, acute HIV syndrome develops in approximately half of infected individuals. This is similar to mononucleosis, and symptoms include headache, fever, sore throat, pharyngitis, erythematous rash, lymphadenopathy and diarrhea. The CD4 lymphocyte count goes down.

About 3 weeks - 3 months after infection, there is an HIV-specific immune response and a decline in HIV viremia (viremia is the presence of virus particles in the blood). Regardless, HIV replication continues. The CD4 lymphocytes count comes back up slightly, but to a level below what it was before infection.

After 10 years (10 years is the median) of latency (in which HIV replication continues), AIDS becomes clinically apparent. This is a result of the immune system's deterioration. The CD4 count falls drastically, and the symptoms of the HIV disease appear: fever, fatigue, weight loss, diarrhea, and persistant lymphadenopathy. Common infections are herpes simplex and oral or vaginal candidiasis. Because the immune system is weak, opportunistic infections by viruses, bacteria, fungi etc. complicate the disease. A person with clinical AIDS dies after an average 2 years.

Transmission

HIV is spread mostly by: AIDS can be passed by contact with blood, semen, or any body fluid that contains visible blood, like faeces, urine and vomit. Thus care should be taken when handling any of the above, or in sharing razor blades, for example.
There is no evidence of HIV being transmitted through saliva, sweat or tears, despite the existence of a small quantity of HIV in these fluids. There are recorded cases of infection from kissing (open mouth), but this is almost certainly due to contact with blood during the kiss. Likewise, there are reported cases in which biting caused an HIV infection, but all these cases involved blood and tissue damage.
There is also no evidence that HIV can be transferred by insect bites.
No one has been identified as infected with HIV due to contact with an environmental surface. Additionally, HIV is unable to reproduce outside its living host. So HIV cannot be transferred through, for example, air, or a toilet seat.

The proper (correct) and consistent (every time!) use of latex condoms when engaging in sexual intercourse - vaginal, anal, or oral - can greatly reduce a person's risk of acquiring or transmitting HIV.




Sources:
  1. http://www.avert.org/origins.htm
  2. http://edcenter.med.cornell.edu
  3. http://medlib.med.utah.edu
  4. http://my.webmd.com
  5. http://thailabonline.com/virus.htm
  6. http://www.niaid.nih.gov/publications/hivaids/hivaids.htm
  7. http://www.accessexcellence.org/AB/GG/hiv.html


*It is widely accepted in the medical and biological world that HIV causes AIDS, and there is evidence for this, but there are skeptics who doubt the causality. It is a controversial issue, and one which I am not going to get into here.

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