HIV-1 Viral Infectivity Factor (Vif) (Vif)

HIV-1 Viral Infectivity Factor (Vif) is a 23 kDa accessory protein essential for the replication of HIV-1 in primary human lymphocytes and macrophages (UniProt: P12504). Its primary biological role is to counteract the host's innate antiviral defense mechanism mediated by APOBEC3G (A3G) and APOBEC3F enzymes, which induce lethal hypermutations in the viral genome (PMID: 12819149). Vif achieves this by acting as an adaptor for a Cullin-5-based E3 ubiquitin ligase complex, targeting A3G for polyubiquitination and subsequent proteasomal degradation (PMID: 15107852). The dimerization of Vif, particularly through its C-terminal PPLP motif (residues 161-164), is critical for its stability and functional interaction with the host machinery (PMID: 11413315). Targeting the Vif dimerization interface or its interactions with host proteins like CBF-beta represents a promising therapeutic strategy to restore A3G activity and suppress viral infectivity (PMID: 22232672). While no Vif inhibitors are currently FDA-approved, several small molecules like RN-18 and various peptidomimetics are under investigation as novel antiretroviral agents (PMID: 18353801).

Other names

Viral infectivity factorp23HIV-1 VifVif dimerization interfaceVif dimerization domain

Inhibition of Vif dimerization or Vif-host protein interactions (e.g., with CBF-beta or Cullin-5) to prevent the degradation of APOBEC3G, thereby restoring the host's innate antiviral defense and inducing viral hypermutation.