distinct determinants in hiv-1 vif and human apobec3 proteins are required for the suppression of diverse host anti-viral proteins不同的决定因素在hiv - 1 vif和人类apobec3蛋白质抑制不同宿主抗病毒蛋白质所必需的.pdfVIP

Distinct Determinants in HIV-1 Vif and Human APOBEC3 Proteins Are Required for the Suppression of Diverse Host Anti-Viral Proteins 1,3 1,4 1 2 1,2 Wenyan Zhang , Gongying Chen , Anna Maria Niewiadomska , Rongzhen Xu , Xiao-Fang Yu * 1 Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, 2 Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China, 3 College of Life Science, Jilin University, Jilin, China, 4 The Sixth Hospital of Hangzhou, Zhejiang, China Abstract Background: APOBEC3G (A3G) and related cytidine deaminases of the APOBEC3 family of proteins are potent inhibitors of many retroviruses, including HIV-1. Formation of infectious HIV-1 requires the suppression of multiple cytidine deaminases by Vif. HIV-1 Vif suppresses various APOBEC3 proteins through the common mechanism of recruiting the Cullin5-ElonginB- ElonginC E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome-mediated degradation. The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition and degradation have not been fully characterized. Methods and Findings: In the present study, we have demonstrated that the regions of APOBEC3F (A3F) that are required for its HIV-1-mediated binding and degradation are distinct from those reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD) of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif-mediated degradation. We also observed that the domains of HIV-1 Vif that are uniquely required f