and the antiviral activity of A3G. However, a recent study by Raja et al has shown that Host AKT-Mediated phosphorylation of HIV-1 Vif at Thr20 stabilizes it to enhance APOBEC3G degradation and potentiate HIV-1 infectivity. HIV-2 Vif2 is only about ∼30% identical at the amino acid level to Vif1, a result of the evolutionary separation in different source species of the two viruses (see Subtypes of HIV). In 2014, it was discovered that Vif2 attaches to A3G and A3F using very different residues compared to Vif1, and that it, unlike Vif1, cannot inhibit A3D at all. In 2016, it was found that Vif2 also attaches to A3C differently. In 2021, it was found that Vif2 inhibits A3B (which HIV-1 does not) and that A3B is able to inhibit a Vif-less HIV-2 (but not a Vif-less HIV-1). As A3B is also implicated in hypermutation in cancer, this discovery could lead to a way to slow down cancer cells. , no structure of Vif2 can be found in the Protein Data Bank. However, it is known from the related Vifmac (SIVmac Vif) that it probably binds A3B in the same orientation as Vif1 does for A3G. Drug target Ever since the 2000s, there has been interest in developing drugs that disarm the virus by inhibiting Vif. An 2018 review lists 17 small molecules capable of stopping viral replication by Vif inhibition, and categorized them into the functional categories of Vif multimerization targeting, A3G-Vif-targeting (two subcategories by the binding interface disrupted), Vif-EloC targeting, and A3G-upregulating. Two of the drugs were further checked for resistance potential. It turns out that the virus can become resistant in laboratory conditions after exposure to increasing amounts of either drug. In July 2021, the Chinese National Medical Products Administration granted conditional approval to azvudine, which claims to be a dual nucleoside reverse transcriptase inhibitor and HIV-1 Vif inhibitor. In other species Vif has been found in other Lentiviruses, including the Simian immunodeficiency virus (SIV), Feline immunodeficiency virus (FIV; ), Visna virus (MVV) and Caprine arthritis encephalitis virus (). The mamallian APOBEC3 enzymes are in an arms race with Vifs found in those viruses, actively evolving and diversifying to escape inactivation. Most Vifs use CBFB with CRL complex (CUL2/5-RBX2-ELOB/C) as the cofactor/adapter, but Visna-maedi virus (MVV) uses CYPA instead of CBFB. Bovine immunodeficiency virus Vif unusually requires none of such adapters. References External links Viral regulatory and accessory proteins