HIV Vpr Protein Upregulates MicroRNA-122 Expression and Stimulates Hepatitis C Virus Replication

Overview

Journal J Gen Virol

Specialty Microbiology

Date 2015 Apr 30

PMID 25920531

Citations 5

Authors

Milin Peng

Xinqiang Xiao

Yan He

Yongfang Jiang

Min Zhang

Feng Peng

Yi Tian

Yun Xu

Guozhong Gong

Affiliations

Soon will be listed here.

Abstract

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.

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References

Amini S, Saunders M, Kelley K, Khalili K, Sawaya B . Interplay between HIV-1 Vpr and Sp1 modulates p21(WAF1) gene expression in human astrocytes. J Biol Chem. 2004; 279(44):46046-56. DOI: 10.1074/jbc.M403792200. View

Sherman M, Schubert U, Williams S, de Noronha C, Kreisberg J, Henklein P . HIV-1 Vpr displays natural protein-transducing properties: implications for viral pathogenesis. Virology. 2002; 302(1):95-105. DOI: 10.1006/viro.2002.1576. View

Thein H, Yi Q, Dore G, Krahn M . Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS. 2008; 22(15):1979-91. DOI: 10.1097/QAD.0b013e32830e6d51. View

Eyster M, Fried M, Di Bisceglie A, Goedert J . Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. Blood. 1994; 84(4):1020-3. View

Macias J, Berenguer J, Japon M, Giron J, Rivero A, Lopez-Cortes L . Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology. 2009; 50(4):1056-63. DOI: 10.1002/hep.23136. View

Jopling C, Yi M, Lancaster A, Lemon S, Sarnow P . Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science. 2005; 309(5740):1577-81. DOI: 10.1126/science.1113329. View

Lin W, Wu G, Li S, Weinberg E, Kumthip K, Peng L . HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive oxygen species and NFkappaB. J Biol Chem. 2010; 286(4):2665-74. PMC: 3024762. DOI: 10.1074/jbc.M110.168286. View

Deng A, Chen C, Ishizaka Y, Chen X, Sun B, Yang R . Human immunodeficiency virus type 1 Vpr increases hepatitis C virus RNA replication in cell culture. Virus Res. 2014; 184:93-102. DOI: 10.1016/j.virusres.2014.02.017. View

Park I, Fan Y, Luo X, Ryou M, Liu J, Green L . HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication. PLoS One. 2014; 9(6):e99545. PMC: 4050050. DOI: 10.1371/journal.pone.0099545. View

10.

Benhamou Y, BOCHET M, Di Martino V, Charlotte F, Azria F, Coutellier A . Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology. 1999; 30(4):1054-8. DOI: 10.1002/hep.510300409. View

11.

Lin W, Weinberg E, Tai A, Peng L, Brockman M, Kim K . HIV increases HCV replication in a TGF-beta1-dependent manner. Gastroenterology. 2008; 134(3):803-11. DOI: 10.1053/j.gastro.2008.01.005. View

12.

Iser D, Warner N, Revill P, Solomon A, Wightman F, Saleh S . Coinfection of hepatic cell lines with human immunodeficiency virus and hepatitis B virus leads to an increase in intracellular hepatitis B surface antigen. J Virol. 2010; 84(12):5860-7. PMC: 2876638. DOI: 10.1128/JVI.02594-09. View

13.

Gupta P, Liu B, Wu J, Soriano V, Vispo E, Carroll A . Genome-wide mRNA and miRNA analysis of peripheral blood mononuclear cells (PBMC) reveals different miRNAs regulating HIV/HCV co-infection. Virology. 2014; 450-451:336-49. DOI: 10.1016/j.virol.2013.12.026. View

14.

Henke J, Goergen D, Zheng J, Song Y, Schuttler C, Fehr C . microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J. 2008; 27(24):3300-10. PMC: 2586803. DOI: 10.1038/emboj.2008.244. View

15.

Conrad K, Giering F, Erfurth C, Neumann A, Fehr C, Meister G . MicroRNA-122 dependent binding of Ago2 protein to hepatitis C virus RNA is associated with enhanced RNA stability and translation stimulation. PLoS One. 2013; 8(2):e56272. PMC: 3566042. DOI: 10.1371/journal.pone.0056272. View

16.

Triboulet R, Mari B, Lin Y, Chable-Bessia C, Bennasser Y, Lebrigand K . Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science. 2007; 315(5818):1579-82. DOI: 10.1126/science.1136319. View

17.

Qu J, Yang Z, Zhang Q, Liu W, Li Y, Ding Q . Human immunodeficiency virus-1 Rev protein activates hepatitis C virus gene expression by directly targeting the HCV 5'-untranslated region. FEBS Lett. 2011; 585(24):4002-9. DOI: 10.1016/j.febslet.2011.11.008. View

18.

Goh W, Rogel M, Kinsey C, Michael S, Fultz P, Nowak M . HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat Med. 1998; 4(1):65-71. DOI: 10.1038/nm0198-065. View

19.

Matthews-Greer J, Caldito G, Adley S, Willis R, Mire A, Jamison R . Comparison of hepatitis C viral loads in patients with or without human immunodeficiency virus. Clin Diagn Lab Immunol. 2001; 8(4):690-4. PMC: 96128. DOI: 10.1128/CDLI.8.4.690-694.2001. View

20.

Frankel A, Pabo C . Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 1988; 55(6):1189-93. DOI: 10.1016/0092-8674(88)90263-2. View