1887

Abstract

Viruses have evolved strategies to overcome the antiviral effects of the host at different levels. Besides specific defence mechanisms, the host responds to viral infection via the interferon pathway and also by RNA interference (RNAi). However, several viruses have been identified that suppress RNAi. We addressed the question of whether hepatitis C virus (HCV) suppresses RNAi, using cell lines constitutively expressing green fluorescent protein (GFP) and inducibly expressing HCV proteins. It was found that short interfering RNA-mediated GFP gene silencing was inhibited when the entire HCV polyprotein was expressed. Further studies showed that HCV structural proteins, and in particular envelope protein 2 (E2), were responsible for this inhibition. Co-precipitation assays demonstrated that E2 bound to Argonaute-2 (Ago-2), a member of the RNA-induced silencing complex, RISC. Thus, HCV E2 that interacts with Ago-2 is able to suppress RNAi.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.2008/002923-0
2008-11-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/11/2761.html?itemId=/content/journal/jgv/10.1099/vir.0.2008/002923-0&mimeType=html&fmt=ahah

References

  1. Andersson M. G., Haasnoot P. C., Xu N., Berenjian S., Berkhout B., Akusjarvi G. 2005; Suppression of RNA interference by adenovirus virus-associated RNA. J Virol 79:9556–9565 [CrossRef]
    [Google Scholar]
  2. Choo Q. L., Kuo G., Weiner A. J., Overby L. R., Bradley D. W., Houghton M. 1989; Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362 [CrossRef]
    [Google Scholar]
  3. Chung C., Park S. G., Park Y. M., Joh J. W., Jung G. 2007; Interferon- γ sensitizes hepatitis B virus-expressing hepatocarcinoma cells to 5-fluorouracil through inhibition of hepatitis B virus-mediated nuclear factor- κ B activation. Cancer Sci 98:1758–1766 [CrossRef]
    [Google Scholar]
  4. Collins R. E., Cheng X. 2006; Structural and biochemical advances in mammalian RNAi. J Cell Biochem 99:1251–1266 [CrossRef]
    [Google Scholar]
  5. Cullen B. R. 2006; Induction of stable RNA interference in mammalian cells. Gene Ther 13:503–508 [CrossRef]
    [Google Scholar]
  6. Englert C., Hou X., Maheswaran S., Bennett P., Ngwu C., Re G. G., Garvin A. J., Rosner M. R., Haber D. A. 1995; WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. EMBO J 14:4662–4675
    [Google Scholar]
  7. Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., Mello C. C. 1998; Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans . Nature 391:806–811 [CrossRef]
    [Google Scholar]
  8. Gosert R., Egger D., Lohmann V., Bartenschlager R., Blum H. E., Bienz K., Moradpour D. 2003; Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J Virol 77:5487–5492 [CrossRef]
    [Google Scholar]
  9. Gossen M., Bujard H. 1992; Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A 89:5547–5551 [CrossRef]
    [Google Scholar]
  10. Ji J., Wernli M., Klimkait T., Erb P. 2003; Enhanced gene silencing by the application of multiple specific small interfering RNAs. FEBS Lett 552:247–252 [CrossRef]
    [Google Scholar]
  11. Ji J., Wernli M., Mielgo A., Buechner S. A., Erb P. 2005; Fas-ligand gene silencing in basal cell carcinoma tissue with small interfering RNA. Gene Ther 12:678–684 [CrossRef]
    [Google Scholar]
  12. 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]
    [Google Scholar]
  13. Kapadia S. B., Brideau-Andersen A., Chisari F. V. 2003; Interference of hepatitis C virus RNA replication by short interfering RNAs. Proc Natl Acad Sci U S A 100:2014–2018 [CrossRef]
    [Google Scholar]
  14. Katze M. G., He Y., Gale M. Jr 2002; Viruses and interferon: a fight for supremacy. Nat Rev Immunol 2:675–687 [CrossRef]
    [Google Scholar]
  15. Kolykhalov A. A., Agapov E. V., Blight K. J., Mihalik K., Feinstone S. M., Rice C. M. 1997; Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science 277:570–574 [CrossRef]
    [Google Scholar]
  16. Li W. X., Li H., Lu R., Li F., Dus M., Atkinson P., Brydon E. W., Johnson K. L., Garcia-Sastre A. other authors 2004; Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing. Proc Natl Acad Sci U S A 101:1350–1355 [CrossRef]
    [Google Scholar]
  17. Liu J., Rivas F. V., Wohlschlegel J., Yates J. R. III, Parker R., Hannon G. J. 2005; A role for the P-body component GW182 in microRNA function. Nat Cell Biol 7:1261–1266 [CrossRef]
    [Google Scholar]
  18. Moradpour D., Englert C., Wakita T., Wands J. R. 1996; Characterization of cell lines allowing tightly regulated expression of hepatitis C virus core protein. Virology 222:51–63 [CrossRef]
    [Google Scholar]
  19. Moradpour D., Kary P., Rice C. M., Blum H. E. 1998; Continuous human cell lines inducibly expressing hepatitis C virus structural and nonstructural proteins. Hepatology 28:192–201
    [Google Scholar]
  20. Moradpour D., Penin F., Rice C. M. 2007; Replication of hepatitis C virus. Nat Rev Microbiol 5:453–463 [CrossRef]
    [Google Scholar]
  21. Morgenstern J. P., Land H. 1990; Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res 18:3587–3596 [CrossRef]
    [Google Scholar]
  22. Morris K. V., Rossi J. J. 2006; Antiviral applications of RNAi. Curr Opin Mol Ther 8:115–121
    [Google Scholar]
  23. Op De Beeck A., Cocquerel L., Dubuisson J. 2001; Biogenesis of hepatitis C virus envelope glycoproteins. J Gen Virol 82:2589–2595
    [Google Scholar]
  24. Pedersen I. M., Cheng G., Wieland S., Volinia S., Croce C. M., Chisari F. V., David M. 2007; Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449:919–922 [CrossRef]
    [Google Scholar]
  25. 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]
    [Google Scholar]
  26. Rossi J. J. 2005; RNAi and the P-body connection. Nat Cell Biol 7:643–644 [CrossRef]
    [Google Scholar]
  27. Schmidt-Mende J., Bieck E., Hugle T., Penin F., Rice C. M., Blum H. E., Moradpour D. 2001; Determinants for membrane association of the hepatitis C virus RNA-dependent RNA polymerase. J Biol Chem 276:44052–44063 [CrossRef]
    [Google Scholar]
  28. Schwarz D. S., Hutvagner G., Du T., Xu Z., Aronin N., Zamore P. D. 2003; Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199–208 [CrossRef]
    [Google Scholar]
  29. Sen G. L., Wehrman T. S., Blau H. M. 2005; mRNA translation is not a prerequisite for small interfering RNA-mediated mRNA cleavage. Differentiation 73:287–293 [CrossRef]
    [Google Scholar]
  30. Takeda A., Sugiyama K., Nagano H., Mori M., Kaido M., Mise K., Tsuda S., Okuno T. 2002; Identification of a novel RNA silencing suppressor, NSs protein of Tomato spotted wilt virus. FEBS Lett 532:75–79 [CrossRef]
    [Google Scholar]
  31. Voinnet O. 2005; Induction and suppression of RNA silencing: insights from viral infections. Nat Rev Genet 6:206–220 [CrossRef]
    [Google Scholar]
  32. Wang Y., Kato N., Jazag A., Dharel N., Otsuka M., Taniguchi H., Kawabe T., Omata M. 2006; Hepatitis C virus core protein is a potent inhibitor of RNA silencing-based antiviral response. Gastroenterology 130:883–892 [CrossRef]
    [Google Scholar]
  33. Watanabe T., Umehara T., Kohara M. 2007; Therapeutic application of RNA interference for hepatitis C virus. Adv Drug Deliv Rev 59:1263–1276 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.2008/002923-0
Loading
/content/journal/jgv/10.1099/vir.0.2008/002923-0
Loading

Data & Media loading...

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