The assembly of Vif ubiquitin E3 ligase for APOBEC3 degradation

Dong Young Kim

APOBEC3G is a cellular antiviral protein that restricts retroviral infection. In non-permissive cells infected by Vif-deficient HIV-1, the protein mediates the hypermutation of viral DNA through the enzymatic activity of cytidine deaminase. To counteract the antiviral activity of APOBEC3G, an accessory protein of HIV-1, Vif, forms ubiquitin E3 ligase through assembly with CUL5-RBX2, ELOB-ELOC and CBFβ. Subsequently, Vif recruits APOBEC3G to the complex as a substrate adaptor of ubiquitin E3 ligase and induces poly-ubiquitination of APOBEC3G for its proteasomal degradation (Fig. 1). This review briefly summarizes current understanding of protein-protein interaction between Vif and host factors required for APOBEC3 degradation, based on high resolution structures of APOBEC3 proteins and Vif-CUL5NTD-ELOBC-CBFβ complex. Fig. 1 A schematic model of assembly of Vif ubiquitin E3 ligase and subsequent APOBEC3 degradation. HIV-1 Vif hijacks cellular E3 ligase components containing CUL5, RBX2, ELOB, ELOC and CBFβ, to poly-ubiquitinate antiviral cellular factors, APOBEC3 proteins. Poly-ubiquitinated APOBEC3 proteins are targeted for proteasomal degradation. Ubiquitin is labeled as Ub.