HIV Vpr protein upregulates microRNA-122 expression and stimulates hepatitis C virus replication.
Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection is characterized by higher serum HCV RNA loads compared with HCV mono-infection. However, the relationship between HIV and HCV replication remains to be clarified. HIV Vpr has been shown to play an essential role in HIV replication. In this study, we aimed to explore the role of Vpr in HCV replication and pathogenesis. We therefore used the genotype 2a full-length HCV strain JFH1 infection system and the genotype 1b full-length HCV replicon OR6 cell line to analyse the effects of Vpr on HCV replication. We found that Vpr promoted HCV 5' UTR activity, HCV RNA replication and HCV protein expression in two HCV infection cell models. Additionally, lymphocyte-produced Vpr significantly induced HCV 5' UTR activity and HCV replication in hepatocytes. We also found that Vpr upregulated the expression of miR-122 by stimulating its promoter activity. Furthermore, an miR-122 inhibitor suppressed the Vpr-mediated enhancement of both HCV 5' UTR activity and HCV replication. In summary, our results revealed that the Vpr-upregulated expression of miR-122 is closely related to the stimulation of HCV 5' UTR activity and HCV replication by Vpr, providing new evidence for how HIV interacts with HCV during HIV/HCV co-infection.
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Milin
M
Peng
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Xinqiang
X
Xiao
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Yan
Y
He
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Yongfang
Y
Jiang
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Min
M
Zhang
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Feng
F
Peng
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Yi
Y
Tian
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Yun
Y
Xu
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Guozhong
G
Gong
D002460:Cell Line; D060085:Coinfection / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D015854:Up-Regulation; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1