Abstract

The HIV-1 accessory protein Vif (virion infectivity factor) is required for the production of infectious virions by CD4(+) lymphocytes. Vif facilitates particle infectivity by blocking the inhibitory activity of APOBEC3G (CEM15), a virion-encapsidated cellular protein that deaminates minus-strand reverse transcript cytosines to uracils. We report that HIV-1 Vif forms a complex with human APOBEC3G that prevents its virion encapsidation. HIV-1 Vif did not efficiently form a complex with mouse APOBEC3G. Vif dramatically reduced the amount of human APOBEC3G encapsidated in HIV-1 virions but did not prevent encapsidation of mouse or AGM APOBEC3G. As a result, these enzymes are potent inhibitors of wild-type HIV-1 replication. The species-specificity of this interaction may play a role in restricting HIV-1 infection to humans. Together these findings suggest that therapeutic intervention that either induced APOBEC3G or blocked its interaction with Vif could be clinically beneficial.