Mechanisms of Immune Evasion by HIV

HIV is the prototype of an infectious pathogen that evades host defenses by destroying the immune system. In addition, several features of HIV may help the virus to evade host immunity.

HIV has an extremely high mutation rate because of error-prone reverse transcription, and in this way it may evade detection by antibodies or T cells generated in response to viral proteins. It has been estimated that in an infected person, every possible point mutation in the viral genome occurs every day. A region of the gp120 molecule, called the V3 loop, is one of the most antigeni-cally variable components of the virus; it varies in HIV isolates taken from the same individual at different times. Furthermore, the regions of the V3 loop that are critical for viral entry and therefore are less frequently mutated are not readily exposed to the humoral immune system.

HIV-infected cells may evade CTLs through down-regulation of class I MHC molecule expression. The HIV Nef protein inhibits expression of class I MHC molecules, mainly by promoting internalization of these molecules. Other mechanisms of inhibiting cell-mediated immunity have been demonstrated in some cases. These include a preferential inhibition of TH1 cytokines, activation of regulatory T cells, and suppression of dendritic cell functions. The mechanisms of these actions of the virus as well as their pathogenic significance are not established.

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