Белок Vif лентивирусов: структура, функции и механизмы противодействия APOBEC3G.

Protein found in lentiviruses
Pfam box
|image=Crystal Structure of the HIV Vif BC box in Complex with Human ElonginB and ElonginC. png
|caption=HIV 1 Vif BC box in Complex with Human ELOB and ELOC .

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 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. as of 2023, 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.

Ever since the 2000s, there has been interest in developing drugs that disarm the virus by inhibiting Vif. 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.

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.