Human immunodeficiency virus type 1 Virion infectivity factor (Vif) – Elongin C (ELOC) interface (HIV-1 Vif–ELOC interface)

The Human immunodeficiency virus type 1 (HIV-1) Virion infectivity factor (Vif) is a critical accessory protein required for viral pathogenesis and replication in vivo (UniProt P12504). Vif's primary role is to counteract the host's innate antiviral defense mediated by APOBEC3 proteins, particularly APOBEC3G, which causes lethal hypermutation of the viral genome during reverse transcription (PubMed 14702096). Vif functions by hijacking a host Cullin-5 (CUL5) E3 ubiquitin ligase complex, where it acts as the substrate recognition subunit. This recruitment is mediated by a direct interaction between the Vif BC-box motif and the host protein Elongin C (ELOC), as well as the recruitment of CBF-beta for complex stability (PubMed 24332710). Furthermore, Vif dimerization via its PPLP motif is essential for the assembly of a functional E3 ligase complex (PubMed 22158918). Targeting the Vif–ELOC interface or the Vif dimerization site with small molecules like RN-18 or peptidomimetics represents a strategy to restore APOBEC3G levels and inhibit HIV-1 (PubMed 18353721). Such therapeutic interventions aim to transition the virus from a productive infection to a restricted state by leveraging the host's own mutational defense mechanisms.

Other names

Vif-ELOC complexVif BC-box interfaceVif dimerization domainVif-Cullin 5 E3 ligase complexVif-ELOC-ELOB-CUL5-CBF-beta complex

Inhibition of the Vif-Elongin C interaction or Vif dimerization to prevent the assembly of the Vif-CUL5 E3 ubiquitin ligase complex, thereby stabilizing host APOBEC3G and promoting viral genome hypermutation.