1. Moloney leukemia virus 10 (MOV10) inhibits the degradation of APOBEC3G through interference with the Vif-mediated ubiquitin–proteasome pathway
- Author
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Feng Huang, Xiaocao Ma, Junsong Zhang, Xinghua Li, Qifei Hu, Jinyu Xia, Cancan Chen, Hui Zhang, Ting Pan, and Chao Liu
- Subjects
lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Proteasome Endopeptidase Complex ,viruses ,Ubiquitin–proteasome system (UPS) ,HIV Infections ,APOBEC-3G Deaminase ,Virus Replication ,Antiviral Agents ,03 medical and health sciences ,Ubiquitin ,Interferon ,Virology ,medicine ,vif Gene Products, Human Immunodeficiency Virus ,Humans ,APOBEC3G ,Cell Line, Transformed ,Infectivity ,biology ,Chemistry ,Research ,virus diseases ,A3G ,Cytidine deaminase ,Vif ,Cell biology ,030104 developmental biology ,Infectious Diseases ,HEK293 Cells ,Viral replication ,Proteasome ,Host-Pathogen Interactions ,Mutation ,biology.protein ,HIV-1 ,MOV10 ,lcsh:RC581-607 ,RNA Helicases ,medicine.drug ,Signal Transduction - Abstract
Background MOV10 protein has ATP-dependent 5′–3′ RNA helicase activity and belongs to the UPF1p superfamily. It can inhibit human immunodeficiency virus type 1 (HIV-1) replication at multiple stages and interact with apolipoprotein-B-mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G), a member of the cytidine deaminase family that exerts potent inhibitory effects against HIV-1 infection. However, HIV-1-encoded virion infectivity factor (Vif) protein specifically mediates the degradation of A3G via the ubiquitin–proteasome system (UPS). Results We demonstrate that MOV10 counteracts Vif-mediated degradation of A3G by inhibiting the assembly of the Vif-CBF-β-Cullin 5-ElonginB-ElonginC complex. Through interference with UPS, MOV10 enhances the level of A3G in HIV-1-infected cells and virions, and synergistically inhibits the replication and infectivity of HIV-1. In addition, the DEAG-box of MOV10 is required for inhibition of Vif-mediated A3G degradation as the DEAG-box mutant significantly loses this ability. Conclusions Our results demonstrate a novel mechanism involved in the anti-HIV-1 function of MOV10. Given that both MOV10 and A3G belong to the interferon antiviral system, their synergistic inhibition of HIV-1 suggests that these proteins may play complicated roles in antiviral functions.
- Published
- 2017