In 1981, the first cases of a new disease now called acquired immune deficiency syndrome (AIDS) were recognized. The victims died of rare infections because their immune systems were crippled. The cause was identified two years later by Luc Montagnier and coworkers. AIDS is produced by human immunodeficiency virus (HIV), of which two major classes are known: HIV-1 and the much less common HIV-2. Like other retroviruses, HIV contains a single-stranded RNA genome that is replicated through a double-stranded DNA intermediate. This viral DNA becomes integrated into the genome of the host cell. In fact, viral genes are transcribed only when they are integrated into the host DNA. The HIV virion is enveloped by a lipid bilayer membrane containing two glycoproteins: gp41 spans the membrane and is associated with gp120, which is located on the external face. The core of the virus contains two copies of the RNA genome and associated transfer RNAs, and several molecules of reverse transcriptase. They are surrounded by many copies of two proteins called p18 and p24. The host cell for HIV is the helper T cell. The gp120 molecules on the membrane of HIV bind to CD4 molecules on the surface of the helper T cell.This interaction allows the associated viral gp41 to insert its amino-terminal head into the host-cell membrane. The viral membrane and the helper cell membrane fuse, and the viral core is released directly into the cytosol. Infection by HIV leads to the destruction of helper T cells because the permeability of the host plasma membrane is markedly increased by the insertion of viral glycoproteins and the budding of virus particles. The influx of ions and water disrupts the ionic balance, causing osmotic lysis. Indeed, the mutation rate of HIV is more than 65 times as high as that of influenza virus. A major aim now is to define relatively conserved sequences in these HIV proteins and use them as immunogens.
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