1887

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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.000169
2015-08-01
2019-12-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/8/2453.html?itemId=/content/journal/jgv/10.1099/vir.0.000169&mimeType=html&fmt=ahah

References

  1. Amini S., Saunders M., Kelley K., Khalili K., Sawaya B.E.. ( 2004;). Interplay between HIV-1 Vpr and Sp1 modulates p21(WAF1) gene expression in human astrocytes. J Biol Chem 279: 46046–46056 [CrossRef] [PubMed].
    [Google Scholar]
  2. Balagopal A., Philp F.H., Astemborski J., Block T.M., Mehta A., Long R., Kirk G.D., Mehta S.H., Cox A.L., other authors. ( 2008;). Human immunodeficiency virus-related microbial translocation and progression of hepatitis C. Gastroenterology 135: 226–233 [CrossRef] [PubMed].
    [Google Scholar]
  3. Beld M., Penning M., Lukashov V., McMorrow M., Roos M., Pakker N., van den Hoek A., Goudsmit J.. ( 1998;). Evidence that both HIV and HIV-induced immunodeficiency enhance HCV replication among HCV seroconverters. Virology 244: 504–512 [CrossRef] [PubMed].
    [Google Scholar]
  4. Benhamou Y., Bochet M., Di Martino V., Charlotte F., Azria F., Coutellier A., Vidaud M., Bricaire F., Opolon P., other authors. ( 1999;). Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Hepatology 30: 1054–1058 [CrossRef] [PubMed].
    [Google Scholar]
  5. Bonacini M., Lin H.J., Hollinger F.B.. ( 2001;). Effect of coexisting HIV-1 infection on the diagnosis and evaluation of hepatitis C virus. J Acquir Immune Defic Syndr 26: 340–344 [CrossRef] [PubMed].
    [Google Scholar]
  6. Conrad K.D., Giering F., Erfurth C., Neumann A., Fehr C., Meister G., Niepmann M.. ( 2013;). MicroRNA-122 dependent binding of Ago2 protein to hepatitis C virus RNA is associated with enhanced RNA stability and translation stimulation. PLoS One 8: e56272 [CrossRef] [PubMed].
    [Google Scholar]
  7. Cribier B., Rey D., Schmitt C., Lang J.M., Kirn A., Stoll-Keller F.. ( 1995;). High hepatitis C viraemia and impaired antibody response in patients coinfected with HIV. AIDS 9: 1131–1136 [CrossRef] [PubMed].
    [Google Scholar]
  8. Deng A., Chen C., Ishizaka Y., Chen X., Sun B., Yang R.. ( 2014;). Human immunodeficiency virus type 1 Vpr increases hepatitis C virus RNA replication in cell culture. Virus Res 184: 93–102 [CrossRef] [PubMed].
    [Google Scholar]
  9. Di Marzio P., Choe S., Ebright M., Knoblauch R., Landau N.R.. ( 1995;). Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr. J Virol 69: 7909–7916 [PubMed].
    [Google Scholar]
  10. Eyster M.E., Fried M.W., Di Bisceglie A.M., Goedert J.J.. ( 1994;). Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. Blood 84: 1020–1023 [PubMed].
    [Google Scholar]
  11. Felzien L.K., Woffendin C., Hottiger M.O., Subbramanian R.A., Cohen E.A., Nabel G.J.. ( 1998;). HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator. Proc Natl Acad Sci U S A 95: 5281–5286 [CrossRef] [PubMed].
    [Google Scholar]
  12. Frankel A.D., Pabo C.O.. ( 1988;). Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55: 1189–1193 [CrossRef] [PubMed].
    [Google Scholar]
  13. Goh W.C., Rogel M.E., Kinsey C.M., Michael S.F., Fultz P.N., Nowak M.A., Hahn B.H., Emerman M.. ( 1998;). HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat Med 4: 65–71 [CrossRef] [PubMed].
    [Google Scholar]
  14. Gupta P., Liu B., Wu J.Q., Soriano V., Vispo E., Carroll A.P., Goldie B.J., Cairns M.J., Saksena N.K.. ( 2014;). Genome-wide mRNA and miRNA analysis of peripheral blood mononuclear cells (PBMC) reveals different miRNAs regulating HIV/HCV co-infection. Virology 450-451: 336–349 [CrossRef] [PubMed].
    [Google Scholar]
  15. Henke J.I., Goergen D., Zheng J., Song Y., Schüttler C.G., Fehr C., Jünemann C., Niepmann M.. ( 2008;). microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J 27: 3300–3310 [CrossRef] [PubMed].
    [Google Scholar]
  16. Ioannou G.N., Bryson C.L., Weiss N.S., Miller R., Scott J.D., Boyko E.J.. ( 2013;). The prevalence of cirrhosis and hepatocellular carcinoma in patients with human immunodeficiency virus infection. Hepatology 57: 249–257 [CrossRef] [PubMed].
    [Google Scholar]
  17. Iser D.M., Warner N., Revill P.A., Solomon A., Wightman F., Saleh S., Crane M., Cameron P.U., Bowden S., other authors. ( 2010a;). 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 84: 5860–5867 [CrossRef] [PubMed].
    [Google Scholar]
  18. Jopling C.L., Yi M., Lancaster A.M., Lemon S.M., Sarnow P.. ( 2005;). Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 309: 1577–1581 [CrossRef] [PubMed].
    [Google Scholar]
  19. Kogan M., Rappaport J.. ( 2011;). HIV-1 accessory protein Vpr: relevance in the pathogenesis of HIV and potential for therapeutic intervention. Retrovirology 8: 25 [CrossRef] [PubMed].
    [Google Scholar]
  20. Levy D.N., Refaeli Y., MacGregor R.R., Weiner D.B.. ( 1994;). Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 91: 10873–10877 [CrossRef] [PubMed].
    [Google Scholar]
  21. Li Z.Y., Xi Y., Zhu W.N., Zeng C., Zhang Z.Q., Guo Z.C., Hao D.L., Liu G., Feng L., other authors. ( 2011;). Positive regulation of hepatic miR-122 expression by HNF4α. J Hepatol 55: 602–611 [CrossRef] [PubMed].
    [Google Scholar]
  22. Lin W., Weinberg E.M., Tai A.W., Peng L.F., Brockman M.A., Kim K.A., Kim S.S., Borges C.B., Shao R.X., Chung R.T.. ( 2008;). HIV increases HCV replication in a TGF-β1-dependent manner. Gastroenterology 134: 803–811 [CrossRef] [PubMed].
    [Google Scholar]
  23. Lin W., Wu G., Li S., Weinberg E.M., Kumthip K., Peng L.F., Méndez-Navarro J., Chen W.C., Jilg N., other authors. ( 2011;). HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive oxygen species and NFκB. J Biol Chem 286: 2665–2674 [CrossRef] [PubMed].
    [Google Scholar]
  24. Macías J., Berenguer J., Japón M.A., Girón J.A., Rivero A., López-Cortés L.F., Moreno A., González-Serrano M., Iribarren J.A., other authors. ( 2009;). Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology 50: 1056–1063 [CrossRef] [PubMed].
    [Google Scholar]
  25. Matthews-Greer J.M., Caldito G.C., Adley S.D., Willis R., Mire A.C., Jamison R.M., McRae K.L., King J.W., Chang W.L.. ( 2001;). Comparison of hepatitis C viral loads in patients with or without human immunodeficiency virus. Clin Diagn Lab Immunol 8: 690–694 [PubMed].
    [Google Scholar]
  26. Mohsen A.H., Easterbrook P.J., Taylor C., Portmann B., Kulasegaram R., Murad S., Wiselka M., Norris S.. ( 2003;). Impact of human immunodeficiency virus (HIV) infection on the progression of liver fibrosis in hepatitis C virus infected patients. Gut 52: 1035–1040 [CrossRef] [PubMed].
    [Google Scholar]
  27. Park I.W., Fan Y., Luo X., Ryou M.G., Liu J., Green L., He J.J.. ( 2014;). HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication. PLoS One 9: e99545 [CrossRef] [PubMed].
    [Google Scholar]
  28. Parodi C., Belmonte L., Bare P., de Bracco M.M., Ruibal-Ares B.. ( 2007;). Impact of human immune deficiency virus infection on hepatitis C virus infection and replication. Curr HIV Res 5: 55–67 [CrossRef] [PubMed].
    [Google Scholar]
  29. Pineda J.A., García-García J.A., Aguilar-Guisado M., Ríos-Villegas M.J., Ruiz-Morales J., Rivero A., del Valle J., Luque R., Rodríguez-Baño J., other authors. ( 2007;). Clinical progression of hepatitis C virus-related chronic liver disease in human immunodeficiency virus-infected patients undergoing highly active antiretroviral therapy. Hepatology 46: 622–630 [CrossRef] [PubMed].
    [Google Scholar]
  30. Poon B., Grovit-Ferbas K., Stewart S.A., Chen I.S.. ( 1998;). Cell cycle arrest by Vpr in HIV-1 virions and insensitivity to antiretroviral agents. 281: 266–269 [CrossRef] [PubMed].
    [Google Scholar]
  31. Qu J., Yang Z., Zhang Q., Liu W., Li Y., Ding Q., Liu F., Liu Y., Pan Z., other authors. ( 2011;). Human immunodeficiency virus-1 Rev protein activates hepatitis C virus gene expression by directly targeting the HCV 5′-untranslated region. FEBS Lett 585: 4002–4009 [CrossRef] [PubMed].
    [Google Scholar]
  32. Qu J., Zhang Q., Li Y., Liu W., Chen L., Zhu Y., Wu J.. ( 2012;). The Tat protein of human immunodeficiency virus-1 enhances hepatitis C virus replication through interferon gamma-inducible protein-10. BMC Immunol 13: 15 [CrossRef] [PubMed].
    [Google Scholar]
  33. Randall G., Panis M., Cooper J.D., Tellinghuisen T.L., Sukhodolets K.E., Pfeffer S., Landthaler M., Landgraf P., Kan S., other authors. ( 2007;). Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci U S A 104: 12884–12889 [CrossRef] [PubMed].
    [Google Scholar]
  34. Sawaya B.E., Khalili K., Mercer W.E., Denisova L., Amini S.. ( 1998;). Cooperative actions of HIV-1 Vpr and p53 modulate viral gene transcription. J Biol Chem 273: 20052–20057 [CrossRef] [PubMed].
    [Google Scholar]
  35. Sherman M.P., Schubert U., Williams S.A., de Noronha C.M., Kreisberg J.F., Henklein P., Greene W.C.. ( 2002;). HIV-1 Vpr displays natural protein-transducing properties: implications for viral pathogenesis. Virology 302: 95–105 [CrossRef] [PubMed].
    [Google Scholar]
  36. Shimakami T., Yamane D., Jangra R.K., Kempf B.J., Spaniel C., Barton D.J., Lemon S.M.. ( 2012;). Stabilization of hepatitis C virus RNA by an Ago2–miR-122 complex. Proc Natl Acad Sci U S A 109: 941–946 [CrossRef] [PubMed].
    [Google Scholar]
  37. Soto B., Sánchez-Quijano A., Rodrigo L., del Olmo J.A., García-Bengoechea M., Hernández-Quero J., Rey C., Abad M.A., Rodríguez M., other authors. ( 1997;). Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. J Hepatol 26: 1–5 [CrossRef] [PubMed].
    [Google Scholar]
  38. Steffan A.M., Lafon M.E., Gendrault J.L., Schweitzer C., Royer C., Jaeck D., Arnaud J.P., Schmitt M.P., Aubertin A.M., Kirn A.. ( 1992;). Primary cultures of endothelial cells from the human liver sinusoid are permissive for human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 89: 1582–1586 [CrossRef] [PubMed].
    [Google Scholar]
  39. Thein H.H., Yi Q., Dore G.J., Krahn M.D.. ( 2008;). 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 22: 1979–1991 [CrossRef] [PubMed].
    [Google Scholar]
  40. Triboulet R., Mari B., Lin Y.L., Chable-Bessia C., Bennasser Y., Lebrigand K., Cardinaud B., Maurin T., Barbry P., other authors. ( 2007;). Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 315: 1579–1582 [CrossRef] [PubMed].
    [Google Scholar]
  41. Zhang H.S., Chen X.Y., Wu T.C., Sang W.W., Ruan Z.. ( 2012;). MiR-34a is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation through the SIRT1/NFκB pathway. FEBS Lett 586: 4203–4207 [CrossRef] [PubMed].
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.000169
Loading
/content/journal/jgv/10.1099/vir.0.000169
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error