HIV-1 Viral Infectivity Factor–Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3 degradation complex (Vif–APOBEC3 complex)

The HIV-1 Vif–APOBEC3 degradation complex is a multi-protein assembly hijacked by the Human Immunodeficiency Virus type 1 (HIV-1) to neutralize host innate immunity (PMID: 24407481). The viral protein Vif (Viral Infectivity Factor) acts as a substrate receptor, bridging host APOBEC3 proteins—specifically APOBEC3G and APOBEC3F—to a Cullin-5-based E3 ubiquitin ligase complex (PMID: 12855938). This complex, which also includes Elongin B, Elongin C, RBX2, and the host cofactor CBF-beta, catalyzes the polyubiquitination of APOBEC3 proteins, leading to their degradation by the 26S proteasome (PMID: 22237107). By depleting these cytidine deaminases, Vif prevents them from being packaged into new virions, where they would otherwise induce lethal G-to-A hypermutations in the viral genome during reverse transcription (PMID: 12134130). Targeting this complex is a significant therapeutic strategy because restoring APOBEC3 activity can effectively restrict viral replication and overcome drug resistance (PMID: 25231446). Experimental inhibitors like RN-18 and VPC-001 aim to disrupt these protein-protein interactions to maintain host restriction factor levels.

Other names

Vif-CUL5-ELOB-ELOC-CBFB complexVif-E3 ubiquitin ligase complexVif-APOBEC3G degradation complexVif-ASB complex

Inhibition of the Vif-mediated recruitment of APOBEC3 proteins to the Cullin-5 E3 ubiquitin ligase complex, thereby preventing the proteasomal degradation of host restriction factors and allowing for viral genome hypermutation (PMID: 25231446).