Immunology of Aids

Although HIV was first identified in 1983, studies of previously stored blood samples indicate that the virus entered the U.S. population sometime in the late 1970s. Worldwide, an estimated 27.9 million people had become HIV-infected through mid-1996, and 7.7 million had developed AIDS, according to the World Health Organization (WHO).

AIDS is a disease of the immune system, and is caused by Human Immuno deficiency Virus (HIV). HIV targets and infects T-helper cells and macrophages. After infection, replication of the virus occurs within the T-helper cells. The cells are lysed and the new viruses are released to infect more T-helper cells. The course of the disease results in the production of massive numbers of virus (1 billion/day) over the full course of the disease. The T- helper cells are infected, and rapidly destroyed both by virus and by cytotoxic T cells. T-helper cells are replaced with nearly a billion produced per day. Over many years (average may be 10), the T-helper cell population is depleted and the body loses its ability to mount an immune response against infections. Thus, we mount a very strong immune response against the virus for a long time, but the virus is produced at a very high rate and ultimately overcomes the ability of the immune system to respond.

Since HIV belongs to a class of viruses called retroviruses, it has genes composed of ribonucleic acid (RNA) molecules. Like all viruses, HIV can replicate only inside host cells, commandeering the cell's machinery to reproduce. However, only HIV and other retroviruses, once inside a cell, use an enzyme called reverse transcriptase to convert their RNA into DNA, which can be incorporated into the host cell's genes. HIV belongs to a subgroup of retroviruses known as lenti-viruses, or "slow" viruses. The course of infection with these viruses is characterized by a long interval, up to 12 years or more, between initial infection and the onset of serious symptoms. Like HIV in humans, there are animal viruses that primarily infect the immune system cells, often causing immuno-deficiency and AIDS-like symptoms. Scientists use these and other viruses and their animal hosts as models of HIV disease.

The CDC currently defines AIDS when one of 25 conditions indicative of severe immuno-suppression associated with HIV infection, such as Pneumocystis carinii pneumonia (PCP) is present, or HIV infection in an individual with a CD4+ T cell count less than 200 cells per cubic millimeter (mm3) of blood.

However, the question that now remains to be answered is 'How does HIV effectively overcome the human immune system?'

In this paper I will try to answer this question. In the first chapter I will explain how HIV is transmitted and what its life cycle looks like. This in order to increase the understanding of how the virus operates. It can be seen as an introductory chapter to the main body of the paper, chapter 2. In the second chapter the specific interactions between the virus and the human immune system will be discussed and shown why its is so threatening. In the last chapter I will deal with certain promising treatments against AIDS.

Among adults, HIV is spread most commonly during sexual intercourse with an infected partner. During sex, the virus can enter the body through the mucosal linings of the vagina, vulva, penis, rectum or, very rarely, via the mouth. The likelihood of transmission is increased by factors that may damage these linings, especially other sexually transmitted diseases that cause ulcers or inflammation.

Research suggests that immune system cells called dendritic cells, which reside in the mucosa, may begin the infection process after sexual exposure by binding to and carrying the virus from the site of infection to the lymph nodes where other cells of the immune system become infected.

HIV also can be transmitted by contact with infected blood, most often by the sharing of drug needles or syringes contaminated with minute quantities of blood containing the virus. The risk of acquiring HIV from blood transfusions is now extremely small in Western countries, as all blood products in these countries are screened routinely for evidence of the virus. Almost all HIV-infected children acquire the virus from their mothers before or during birth.

HIV has a diameter of 1/10,000 of a millimeter and is spherical in shape. The outer coat of the virus, known as the viral envelope, is composed of lipid bi-layer, taken from the membrane of a human cell when a newly formed virus particle buds from the cell. Embedded in the viral envelope are proteins from the host cell, as well as 72 copies (on average) of a complex HIV protein that protrudes from the envelope surface. This protein, known as Env, consists of a cap made of three or four molecules called glycoprotein (gp) 120, and a stem consisting of three or four gp41 molecules that anchor the structure in the viral envelope.

Within the envelope of a mature HIV particle is a bullet-shaped core or capsid, made of 2000 copies of another viral protein, p24. The capsid surrounds two single strands of HIV RNA, each of which has a copy of the virus's nine genes. Three of these, gag, pol and env, contain information needed to make structural proteins for new virus particles. The env gene, for example, codes for a protein called gp160 that is broken down by a viral enzyme to form gp120 and gp41, the components of Env.

Three regulatory genes, tat, rev and nef, and three auxiliary genes, vif, vpr and vpu, that contain the information necessary for the production of proteins that control the ability of HIV to infect a cell, produce new copies of virus or cause disease. The protein encoded by nef, for instance, appears necessary for the virus to replicate efficiently, and the vpu-encoded protein influences the release of new virus particles from infected cells.

When HIV encounters its target cell, the external glycoprotein portion of the viral envelope (GP120) binds with high affinity to the extra cellular component of the receptor protein CD 4, present on helper lymphocytes(Helper T cells).

The membrane portion of the viral envelope fuses to the lymphocyte membrane and the virus is expelled into the cell. Then the reverse transcriptase of the virus copies the RNA into DNA.

Once the DNA is integrated into the host cell genome, the presence of HIV has become a permanent part of the lymphocyte (Helper T).

The viral production proceeds through a complex set of highly regulated steps. First, messenger RNA of the virus and viral proteins are produced. Proteins are then modified by a viral protease to become mature