Multifaceted HIV‐1 Vif interactions with human E3 ubiquitin ligase and APOBEC3s

• DOI: 10.1111/febs.15550
• Publication Date: 2020-09-14T07:55:20Z
• Authors: Yingxia Hu; Kirsten M. Knecht; Qi Shen; Yong Xiong
• Keywords: 0301 basic medicine; Protein Conformation; Ubiquitin-Protein Ligases; Ubiquitination; Virion; HIV Infections; Core Binding Factor beta Subunit; 3. Good health; 03 medical and health sciences; Host-Pathogen Interactions; HIV-1; vif Gene Products, Human Immunodeficiency Virus; Humans; APOBEC Deaminases; Protein Binding

APOBEC3 (A3) proteins are a family of host antiviral restriction factors that potently inhibit various retroviral infections, including human immunodeficiency virus (HIV)‐1. To overcome this restriction, HIV‐1 virion infectivity factor (Vif) recruits the cellular cofactor CBFβ to assist in targeting A3 proteins to a host E3 ligase complex for polyubiquitination and subsequent proteasomal degradation. Intervention of the Vif‐A3 interactions could be a promising therapeutic strategy to facilitate A3‐mediated suppression of HIV‐1 in patients. In this structural snapshot, we review the structural features of the recently determined structure of human A3F in complex with HIV‐1 Vif and its cofactor CBFβ, discuss insights into the molecular principles of Vif‐A3 interplay during the arms race between the virus and host, and highlight the therapeutic implications.