Viral infectivity factor, or Vif, is an accessory protein found in HIV and other lentiviruses. Its role is to disrupt the antiviral activity of the human enzyme APOBEC (specifically APOBEC3G, "A3G" in short, and other A3 enzymes) by targeting it for ubiquitination and cellular degradation. APOBEC is a cytidine deaminase enzyme that mutates viral nucleic acids. Despite the functional and (weak) structural similarities, Vif found in lentiviruses can function in quite different ways. For example, the HIV-1 Vif ("Vif1" hereafter) and HIV-2 Vif ("Vif2") attach to APOBEC from different ends of themselves and have a different spectrum of inhibition. As HIV-1 is older and more virulent, many more studies have been done on the Vif1 than on the Vif2. Similarly, more studies have been done on the HIV/SIV Vif than on any other lentiviral Vif. Mechanism HIV-1 Vif1 is a 23-kilodalton protein that is essential for viral replication. Vif1 inhibits the cellular protein, APOBEC3G, from entering the virion during budding from a host cell by targeting it for proteasomal degradation. Vif1 binds to A3G as well as the cellular Cullin5 E3 Ubiquitin Ligase (ELOB-ELOC-CUL5) and a CBFB cofactor so that the ligase can be hijacked to tag A3G for degradation. The crystal Structure of the HIV-1 Vif BC-box in Complex with Human Elongin B and Elongin C was solved in 2008, and the structure of the full Vif1/E3 complex was solved in 2014. 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. Vif1 is additionally able to inhibit human A3C, A3D, A3F, and A3H haplotype II, all of which can similarly be packaged and cause hypermutation in Vif-deficient HIV-1. Different surfaces on Vif1 are used to bind A3C, A3F, and A3G. Vif may still be able to inhibit A3 in ways independent of degradation. Vif1 seems to reduce the amount of A3 proteins (including A3D/G/F) packaged in the virion, and to slow down the action of any A3G that does make it in. Vif1 was considered as a phosphoprotein and phosphorylation seemed to be required for viral infectivity. But recent studies with the use of metabolic labelling demonstrated that serine/threonine phosphorylation of Vif1 and A3G is not required for the interaction of Vif1 with A3G for Vif dependent degradation of A3G