HIV can attack a variety of types of cells in the human body, but most critically a subset of lymphocytes, the T-helper (Th) cells. These cells possess the CD4 surface protein to which the virus attaches, and they are referred to as CD4+ cells. In order for the virus to enter the cell, it must also attach to certain cytokine receptors on the cell surface. Following entry of the virus, a DNA copy is made using reverse transcriptase. This copy integrates itself into the cell's genome and hides there, inaccessible to antiviral chemotherapy. If the cell becomes activated, however, the virus leaves the cell genome, replicates, and destroys the cell, releasing virions to infect additional cells. Despite the body's ability to replace hundreds of billions of CD4+ lymphocytes, the number of these lymphocytes slowly declines over many months or years. Infection of macrophages contributes to the decline in cellular immunity. Macrophages, also vitally important to the immune system, are also CD4+ cells. Although they are generally not killed, their function is impaired both by the viral infection and the lack of interaction with Th lymphocytes. Eventually, the immune system becomes so impaired it can no longer respond to infections or cancers. ■ T-helper cells, p. 394 ■ macrophages, p. 377

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