Viral infectivity factor
Viral infectivity factor, or Vif, is a protein found in HIV and other retroviruses. Its role is to disrupt the antiviral activity of the human enzyme APOBEC (See also APOBEC3G) by targeting it for ubiquitination and cellular degradation. APOBEC is a cytidine deaminase enzyme that mutates viral nucleic acids.
Vif is a 23-kilodalton protein that is essential for viral replication. Vif inhibits the cellular protein, APOBEC3G, from entering the virion during budding from a host cell by targeting it for proteasomal degradation. Vif hijacks the cellular Cullin5 E3 ubiquitin ligase, which is composed of ElonginB, ElonginC, Cullin5, and Rbx2, (Crystal Structure of the HIV Vif BC-box in Complex with Human ElonginB and ElonginC is solved and shown here) in order to target APOBEC3G for degradation. In the absence of Vif, APOBEC3G causes hypermutation of the viral genome, rendering it dead-on-arrival at the next host cell. APOBEC3G is thus a host defence to retroviral infection which HIV-1 has overcome by the acquisition of Vif. Targeting vif has been suggested as a strategy for future HIV drug therapies.
Vif was considered as a phospho-protein and phosphorylation seemed to be required for viral infectivity. But recent studies with the use of metabolic labelling demonstrated that serine/threonine phosphorylation of Vif and A3G is not required for the interaction of Vif with A3G for Vif dependent degradation of A3G and the antiviral activity of A3G.
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