• HIV Pathogenesis

    HIV is an RNA virus that contains a unique enzyme called reverse transcriptase, which allows the HIV-RNA to make a template for a provirus that allows the "bad" RNA to integrate into the nucleus of the CD4 cell. Other important pathogenic proteins include the P24 core protein, which is what is detected in the enzyme-linked immunoassay (EIA) and western blot for the diagnosis of HIV infection; and the surface protein GP120, which is important for attachment and entry of the virus into the CD4 helper lymphocyte. The GP 41 transmembrane protein is also important for HIV pathogenesis. These glycoproteins assist in diagnosing HIV infection by the confirmatory western blot test. To enter the cell, the HIV virus needs to attach to the CD4 T helper cell receptor as well as the co-receptor on the surface of the T cell (CCR5 or CXCR4). Some individuals, particularly Caucasians of North American and European descent, may not have the genes for this co-receptor. These people may be more resistant to HIV infection of their T cells or more immune to infection with the virus.

      The Structure of HIV

    Once attachment of the HIV virus is made to the CD4 lymphocyte, the virus is able to fuse with the membrane of the CD4 cell and enter the cytoplasm of the cell. Upon entering the cell, reverse transcriptase is used to make a DNA template, or provirus, for entry into the nucleus of the CD4 cell. The nuclear entry is facilitated by the presence of an enzyme called integrase. Once the provirus is integrated into the nucleus of the cell, the cell is changed from an immune protective cell to a factory for making more HIV virus particles. The assembled cell manufactures proteins and glycoproteins and with the presence of another enzyme, viral protease, the virus is prepared for final assembly and release. Possible targets for antiretroviral intervention include blocking the virus's entry into the cell and the inhibition of the three HIV enzymes (reverse transcriptase, integrase, protease).

    Currently, the main drugs for therapy are targeted at inhibiting HIV reverse transcriptase and HIV protease. With further research and development, additional drugs will soon be available to prevent entry of the virus (fusion inhibitors) and inhibit HIV integrase.

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