title: HIV-1 Vpr increases HCV replication through VprBP in cell culture.
abstract: Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs at a high frequency, in which HIV shows a promotion of HCV-derived liver diseases. However, the mechanism of how this occurs is not well understood. Our previous work has demonstrated that the HIV-1 accessory protein Vpr enhances HCV RNA replication in cell culture. Because Vpr performs most of its functions through host protein VprBP (DCAF1), the role of VprBP in the regulation of HCV by Vpr was investigated in this study. We found that the Vpr mutant Q65R, which is deficient in VprBP binding, could not enhance HCV replication. Furthermore, Vpr-mediated enhancement of HCV replication was severely diminished in VprBP knockdown cells. In addition, an inhibitor of Cullin RING E3 ligases, MLN4924, impaired the function of Vpr during HCV replication. Together, these results suggest that Vpr promotes HCV replication in a VprBP-dependent manner, and that the activity of Cullin RING E3 ligases is essential to this process. In conclusion, our findings demonstrate that HIV-1 Vpr makes the cellular environment more suitable for HCV replication, which might relate with the host ubiquitination system.
authors.affiliation: Research Group of HIV Molecular Epidemiology and Virology, Center for Molecular Virology, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Research Group of HIV Molecular Epidemiology and Virology, Center for Molecular Virology, 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 Molecular Virology, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yuan
authors.affiliation: Research Group of HIV Molecular Epidemiology and Virology, Center for Molecular Virology, 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 Molecular Virology, 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: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D060085:Coinfection; D055785:Gene Knockdown Techniques; D016679:Genome, Viral; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000378:metabolism / Q000821:virology; D006801:Humans; D056265:Microbial Interactions; D009154:Mutation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D012367:RNA, Viral / Q000235:genetics; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D012367:RNA, Viral; 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
keywords: Cullin RING E3 ligases; HCV; HIV-1; Vpr; VprBP