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Pharmacology => Drug => Human Immunodeficiency Virus (HIV)
Human Immunodeficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), virus of the retrovirus family, the agent that causes acquired immune deficiency syndrome (AIDS). A person infected with HIV gradually loses the function of their immune system and becomes vulnerable to numerous infections that define AIDS. The retrovirus HIV was discovered in association with AIDS almost simultaneously by three separate research teams. French virologist Luc Montagnier and scientists at the Pasteur Institute in Paris discovered it in 1983, American virologist Robert Gallo and his colleagues at the National Cancer Institute in Bethesda, Maryland, in 1984, and, also in 1984, American immunologist Jay Levy and his colleagues at the University of California in San Francisco.
Retroviruses undergo a long incubation period before the onset of disease, during which time they infect blood cells and the nervous system and suppress the immune system. In order to replicate or reproduce, however, retroviruses must convert ribonucleic acid (RNA-the genetic material of the retrovirus) in their genes into deoxyribonucleic acid (DNA-the genetic material of normal body cells). This process, known as reverse transcription, is accomplished using an enzyme called reverse transcriptase, which is carried by the retroviruses.
The outer surface of HIV is a lipid, or fatty, envelope. Protruding from the surface of the envelope are the viral transmembrane glycoprotein (gp41) and the envelope glycoprotein (gp120)-two proteins that enable HIV to bind and fuse with a target cell. Within the envelope, the virus particle is composed of a viral core protein known as p17 and another core protein known as p24 that forms an inner, cylindrically shaped nucleoid (the area in which the genetic material is contained). The nucleoid contains two strands of viral RNA and the associated reverse transcriptase enzyme.
HIV infects cells that carry the CD4 molecule on their outer membranes, such as CD4 T-lymphocytes (a type of white blood cell). CD4 is a normal immune protein that HIV uses as the major receptor to which it attaches. The viral gp120 specifically recognizes and binds to CD4, causing the virus to fuse with the cell membrane. Fusion permits the viral nucleoid to enter the cell. Reverse transcription then occurs, and the viral RNA is converted into DNA. The viral DNA is transported to the cell nucleus and inserted into the cell's DNA. Using the replication machinery of the host cell, this viral DNA is transcribed to make messenger RNA (mRNA) and new strands of viral RNA-the two components necessary to assemble new virus particles. The new HIV particles are released by budding from the cell surface, taking a piece of the cell's membrane as their envelope.
Binding to CD4 alone, however, is not enough to enable HIV to enter the host target cell. The virus must also attach to small proteins called chemokine receptors that are also present on the surface of human immune cells. Researchers identified two receptors for chemokines involved in HIV entry in 1996: CXCR4, which is bound by HIV strains that dominate during the latter stages of the disease; and CCR5, which is bound by HIV strains that dominate in the early stages of the disease. Additional chemokine receptors are continuously being discovered.
HIV replication can kill CD4 T-lymphocytes. The loss of these cells paralyzes the immune system and is one mechanism by which HIV infection causes AIDS. As researchers learn more about the chemical structure of HIV and the mechanisms it uses for replication, the likelihood of a vaccine or cure increases. In 1998, the first large-scale trial of an HIV vaccine was initiated. The vaccine, made from the viral protein gp120, is designed to stimulate the production of antibodies that could protect against HIV infection. The safety and effectiveness of the vaccine will be tested on uninfected volunteers in Thailand and North America.
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