This chapter describes recent advances in understanding the molecular mechanisms by which HIV-1 infection produces immunodeficiency, focusing in particular on quantitative and qualitative defects in the CD4 + T cell compartment. Two questions are considered in detail. First, what causes the loss of CD4 + T cells in HIV-1 infection. Second, what factors are responsible for the functional defects observed in those CD4 + T cells that are not depleted. The chapter also illustrates steps involved in the mechanism of infection. HIV-1 attaches to CD4 + T cells following high-affinity interactions between the gp120 subunit of the env protein and CD4. Binding to CD4 induces a conformational change in gp120 that allows binding of gp120 to co-receptors. Binding of gp120 to co-receptor induces a further conformational change in the gp120-gp41 complex, resulting in exposure of the N-terminal hydrophobic domain of gp41. This hydrophobic domain inserts into the target cell membrane. Finally, the viral envelope fuses with the plasma membrane and viral capsid delivers into the cytoplasm of the CD4 + T cell.
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