Vif and the Identification of a Host Restriction Factor for HIV1

In the years following the identification of HIV as the causative agent of acquired immune deficiency syndrome (AIDS) (Barré-Sinoussi et al., 1983; Gallo et al., 1983), the function of most of HIV's nine genes was rapidly identified. The function of HIV-1 vif gene product (virion infectivity factor), however, long remained elusive. Vifencodes a 23-kDa protein that is essential under physiological conditions for the production of infectious virions from the integrated HIV provirus. It was soon discovered, however, that Vif was not required for the production of infectious particles in various laboratory T-cell lines (Gabuzda et al., 1992). T-cell lines could then be segregated in two categories depending if they were permissive or nonpermissive for the production of infectious HIV particles in the absence of a functional vif gene. Since the expression of Vif is essential only in the virus producer cell, it was then speculated that nonpermissive T cells either lacked an essential component for the production of infectious viral particles or expressed a factor that needed to be neutralized by Vif (Gabuzda et al., 1992; Simon and Malim, 1996; von Schwedler et al., 1993). The answer to this enigma came much later by the identification in nonpermissive cells of an innate antiretroviral factor initially named CEM15 (Sheehy et al., 2002) and subsequently recognized as identical to the APOBEC3G (Jarmuz et al., 2002). The ultimate demonstration that APOBEC3G was indeed responsible for restricting HIV infection came with an experiment showing that enforced expression of APOBEC3G in permissive CEM-SS cells reverted these to a nonpermissive phenotype (Sheehy et al., 2002).

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