Viral infectivity factor (Vif) (Vif)

The HIV-1 Vif protein, or viral infectivity factor, is a 23-kDa accessory protein composed of 192 amino acids that plays a critical role in counteracting the host's innate antiviral defenses during HIV-1 replication. Vif binds to host APOBEC3 proteins such as APOBEC3G (A3G), APOBEC3F (A3F), A3C, A3D, and A3H haplotype II, recruiting them to a Cullin5-based E3 ubiquitin ligase complex (including ELOB, ELOC, RBX2, and CBF-β) for proteasomal degradation, thereby preventing their packaging into virions and subsequent hypermutation of the viral genome. In the absence of Vif, A3G incorporates into budding virions and induces G-to-A hypermutations, rendering the virus non-infectious. Vif also exhibits RNA chaperone activity by specifically binding HIV-1 genomic RNA in the cytoplasm to form a 40S mRNP complex, potentially protecting viral RNA and facilitating its interaction with Gag precursors. Structurally, Vif features motifs like the HCCH zinc-binding domain, BC box, and PPLP motif that enable interactions with A3 proteins via electrostatic and hydrophobic interfaces, as well as oligomerization. Beyond A3 antagonism, Vif contributes to HIV-1 pathogenesis by inducing p53-dependent G2 cell cycle arrest, optimizing viral replication in non-dividing cells. As a viral protein essential for infectivity in primary T cells and macrophages, Vif represents a promising therapeutic target for disrupting HIV-1 replication, though no approved drugs directly target it yet.

Other names

Virion infectivity factor