title: HIV-1 Vpr suppresses the cytomegalovirus promoter in a CRL4(DCAF1) E3 ligase independent manner.
abstract: Although the Vpr protein of human immunodeficiency virus type 1 (HIV-1) has been shown to act as a transcriptional activator of the HIV-1 LTR and certain host genes, the current study demonstrates that it can also function as a potent inhibitor of the cytomegalovirus (CMV) promoter. Previous studies have shown that the cell cycle arrest and apoptotic functions of Vpr required recruitment of the CRL4(DCAF1) E3 ligase, but this complex is shown not to be required for inhibition of the CMV promoter. We identified conserved sites (A30/V31) from diverse Vpr from HIV/SIV that were critical for blocking the CMV promoter activity. Interestingly, the Vpr mutant A30S/V31S protein also impaired the ability of Vpr to down-regulate transcription of the host UNG2 gene. Our findings shed light on the dual functions of Vpr on the transcription of HIV-1, other viruses and host genes which may contribute to viral replication and disease progression in vivo.
authors.affiliation: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130061, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 30072, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Guo
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 30072, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Markham
authors.affiliation: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130061, China; School of Life Sciences, Tianjin University, Tianjin 30072, China; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: wwei6@jhu.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130061, China; School of Life Sciences, Tianjin University, Tianjin 30072, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: xfyu@tju.edu.cn.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics; D057809:HEK293 Cells; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C429530:DTL protein, human; D050505:Mutant Proteins; D009687:Nuclear 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; C492570:CCNO protein, human; D045647:DNA Glycosylases
keywords: CMV; HIV-1; Transcriptional regulation; UNG2; Vpr