Lessons in HIV

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		HIV Life Cycle Real Video: Streaming QuickTime: Cable/DSL | Modem
		Fusion and Cell Entry Real Video: Streaming QuickTime: Cable/DSL | Modem
		Attachment Inhibition Real Video: Streaming QuickTime: Cable/DSL | Modem
		Co-Receptor Inhibition Real Video: Streaming QuickTime: Cable/DSL | Modem
		Fusion Inhibition Real Video: Streaming QuickTime: Cable/DSL | Modem

Human immunodeficiency virus is a spherical retrovirus of 100 nm in diameter. This shape is defined by three structures: a lipidic external membrane, a matrix and a nucleocapsid that contains the viral genome. The genetic information of HIV is stored in two RNA chains. The viral genome codes for several genes that yield different viral proteins with well defined functions.

The external protein of HIV (gp120) binds to the CD4 protein, which is found on the surface of the lymphocytes T4 and macrophages. This fact allows HIV to infect and destroy T4 lymphocytes.
The first step in HIV life cycle is the attachment of viral particles to the cell. The protein gp120 interacts with CD4 and then with a second protein of the cell surface (the chemokine receptor CXCR4 or CCR5) allowing the fusion of viral and cellular membranes mediated by gp41. After membrane fusion, the viral core enters the cell and the viral RNA is released. The viral genome (RNA) is then retrotranscribed (converted to DNA) by the viral enzyme RT and integrated into the cellular DNA by the viral enzyme Integrase. Once the viral genome is integrated, the cell cannot identify it as an external DNA, and the cellular machinery produces viral proteins. These proteins will be assembled to form new HIV particles, which will be released by the cells and maturated by the viral protease. These newly formed partivles are now ready to infect new cells.
The infection of one cell by one HIV particle may result in the production of thousands of new infectious viral particles.

Our immune system is able to identify and to destroy external pathogens. The proper function of the immune system requires a complex equilibrium between different cell types. Among them, a special class of lymphocytes, the so-called lymphocytes T4 or CD4 play a key role in the establishment and the maintenance of immune responses. The destruction of CD4 cells by HIV infection is the cause of the immunodeficiency associated to HIV.
After the first contact with the virus (primoinfection) there is an almost free viral replication that results in viral levels (viral load) of 106-107 copies of RNA per ml. Ussually, infected people require several days to organize an immune response that will control HIV replication (seroconversion). However the immune control of HIV replication is not complete and there is a slow but progressive destruction of CD4 T cells, which finally will weaken and break down the immune function. This is the onset of AIDS.

The intensive research in the HIV field has given a collection of drugs that can block HIV replication. At this moment there are two main groups of anti-HIV drugs. The first one is the the family of inhibitors of the viral enzyme reverse transcriptase that block the conversion of the viral RNA into DNA, thereby blocking HIV infection. The second one is the family of inhibitors of the viral enzyme protease, developed in 1995 that block the maturation of viral particles.
Although HIV can evolve to elude the action of drugs (development of resistance) and there are side effects after long periods of treatment, the combination of several drugs in tritherapy has drastically reduced the impact of AIDS and the mortality in patients infected by HIV.