Human immunodeficiency virus type 1 Virion infectivity factor (Vif) (Vif)

The HIV-1 Virion infectivity factor (Vif) is a 23 kDa accessory protein essential for viral pathogenesis and replication in primary human T-cells (UniProt P12504). Its primary biological function is to counteract the host's innate antiviral restriction factors, specifically the APOBEC3 family of cytidine deaminases, such as APOBEC3G and APOBEC3F (PubMed: 12110894). Vif acts as a molecular bridge, recruiting a host E3 ubiquitin ligase complex consisting of Cullin-5, Elongin B, Elongin C, and Core-binding factor subunit beta (CBFβ) to trigger the polyubiquitination and subsequent proteasomal degradation of APOBEC3G (PubMed: 22190034). In the absence of Vif, APOBEC3G is packaged into progeny virions and induces lethal hypermutation of the viral genome during reverse transcription in the next target cell. Because Vif is critical for overcoming this natural defense, it is a highly attractive target for antiretroviral therapy. Current drug discovery efforts focus on small molecules that disrupt the interaction between Vif and its host co-factors or the Vif-APOBEC3G interface to restore the cell's innate ability to restrict HIV-1 (PubMed: 18334635).

Other names

Virion infectivity factorp23HIV-1 VifVif protein

Inhibition of Vif-mediated degradation of APOBEC3G by disrupting the Vif-APOBEC3G interaction or the assembly of the Vif-Cul5-CBFβ E3 ubiquitin ligase complex.