08-29-2021-2031 - Viral infectivity factor Vif BC Vif HIV

Viral infectivity factor

HIV Vif BC-box in Complex with Human ELOB and ELOC (PDB: 3DCG​).[1]
Identifiers
Symbol Vif
Pfam PF00559
InterPro IPR000475


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) 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 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.[2] The crystal Structure of the HIV Vif BC-box in Complex with Human Elongin B and Elongin C was solved in 2008,[1] and the structure of the full Vif/E3 complex was solved in 2014.[3] 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.[4]

Vif was considered as a phosphoprotein and phosphorylation seemed to be required for viral infectivity.[5][6]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.[7]
In other species[edit]

Vif has been found in other Lentiviruses, including the Simian immunodeficiency virus (SIV), Feline immunodeficiency virus (FIV; Pfam PF05851), Visna virus (MVV) and Caprine arthritis encephalitis virus (Pfam PF07401).[8][9] The mamallian APOBEC3 enzymes are in an arms race with Vifs found in those viruses, actively evolving and diversifying to escape inactivation. Some Vifs use CYPA instead of CBFB.[10][11][12]
showAvailable protein structures:

https://en.wikipedia.org/wiki/Viral_infectivity_factor

above. 

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