title: The HIV-1 accessory protein Vpr induces the degradation of the anti-HIV-1 agent APOBEC3G through a VprBP-mediated proteasomal pathway.
abstract: The host anti-HIV-1 factor APOBEC3G (A3G) plays a potential role in restricting HIV-1 replication, although this antagonist can be encountered and disarmed by the Vif protein. In this paper, we report that another HIV-1 accessory protein, viral protein R (Vpr), can interact with A3G and intervene in its antiviral behavior. The interaction of Vpr and A3G was predicted by computer-based screen and confirmed by a co-immunoprecipitation (Co-IP) approach. We found that Vpr could reduce the virion encapsidation of A3G to enhance viral replication. Subsequent experiments showed that Vpr downregulated A3G through Vpr-binding protein (VprBP)-mediated proteasomal degradation, and further confirmed that the reduction of A3G encapsidation associated with Vpr was due to Vpr's degradation-inducing activity. Our findings highlight the versatility of Vpr by unveiling the hostile relationship between Vpr and A3G. In addition, the observation that A3G is targeted to the proteasomal degradation pathway by Vpr in addition to Vif implicates the existence of crosstalk between different HIV-1-host ubiquitin ligase complex systems.
authors.affiliation: Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, PR China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, PR China. Electronic address: sunbl@wh.iov.cn.
authors.forename: Binlian
authors.initials: B
authors.lastname: Sun
authors.affiliation: Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, PR China. Electronic address: ryang@wh.iov.cn.
authors.forename: Rongge
authors.initials: R
authors.lastname: Yang
mesh_terms: D000071480:APOBEC-3G Deaminase; D002352:Carrier Proteins / Q000378:metabolism*; D019295:Computational Biology; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D047468:Immunoprecipitation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D059748:Proteolysis; D044767:Ubiquitin-Protein Ligases; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D044767:Ubiquitin-Protein Ligases; C530533:DCAF1 protein, human; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase
keywords: APOBEC3G (A3G); Degradation; Encapsidation; HIV-1; Vpr; VprBP