HIV-1 Vpr suppresses the cytomegalovirus promoter in a CRL4(DCAF1) E3 ligase independent manner

Xianjun Liu; Haoran Guo; Hong Wang; Richard Markham; Wei Wei; Xiao-Fang Yu

doi:10.1016/j.bbrc.2015.02.060

HIV-1 Vpr suppresses the cytomegalovirus promoter in a CRL4(DCAF1) E3 ligase independent manner

Biochem Biophys Res Commun. 2015 Apr 3;459(2):214-219. doi: 10.1016/j.bbrc.2015.02.060. Epub 2015 Feb 19.

Authors

Xianjun Liu¹, Haoran Guo², Hong Wang³, Richard Markham⁴, Wei Wei⁵, Xiao-Fang Yu⁶

Affiliations

¹ First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province 130061, China.
² School of Life Sciences, Tianjin University, Tianjin 30072, China; Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China.
³ School of Life Sciences, Tianjin University, Tianjin 30072, China.
⁴ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
⁵ 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.
⁶ 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.

PMID: 25704090
DOI: 10.1016/j.bbrc.2015.02.060

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.

Keywords: CMV; HIV-1; Transcriptional regulation; UNG2; Vpr.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carrier Proteins / metabolism
Cytomegalovirus / genetics*
DNA Glycosylases / genetics
HEK293 Cells
HIV Long Terminal Repeat
HIV-1 / genetics*
HIV-1 / metabolism*
HIV-1 / pathogenicity
HeLa Cells
Host-Pathogen Interactions / genetics
Humans
Models, Molecular
Mutant Proteins / genetics
Mutant Proteins / metabolism
Mutation
Nuclear Proteins / metabolism
Promoter Regions, Genetic*
Protein Conformation
Protein Serine-Threonine Kinases
Ubiquitin-Protein Ligases / metabolism
vpr Gene Products, Human Immunodeficiency Virus / chemistry
vpr Gene Products, Human Immunodeficiency Virus / genetics*
vpr Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

Carrier Proteins
DTL protein, human
Mutant Proteins
Nuclear Proteins
vpr Gene Products, Human Immunodeficiency Virus
vpr protein, Human immunodeficiency virus 1
Ubiquitin-Protein Ligases
DCAF1 protein, human
Protein Serine-Threonine Kinases
CCNO protein, human
DNA Glycosylases