Journal of Hepatology
Volume 52, Issue 2 , Pages 183-190 , February 2010

Hepatitis C virions subvert natural killer cell activation to generate a cytokine environment permissive for infection

  • Stefania Crotta

      Affiliations

    • Department of Microbial Molecular Biology, Novartis Vaccines and Diagnostics, via Fiorentina 1, 53100 Siena, Italy
    • Corresponding Author InformationCorresponding author. Present address: Division of Immunoregulation, National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA London, UK. Tel.: +44 02089593666x2260.
  • ,
  • Michela Brazzoli

      Affiliations

    • Department of Immunology, Novartis Vaccines and Diagnostics, via Fiorentina 1, 53100 Siena, Italy
  • ,
  • Diego Piccioli

      Affiliations

    • Department of Immunology, Novartis Vaccines and Diagnostics, via Fiorentina 1, 53100 Siena, Italy
  • ,
  • Nicholas M. Valiante

      Affiliations

    • Department of Immunology, Novartis Vaccines and Diagnostics, 45 Sidney Street, Cambridge, MA 02139, USA
  • ,
  • Andreas Wack

      Affiliations

    • Department of Immunology, Novartis Vaccines and Diagnostics, via Fiorentina 1, 53100 Siena, Italy
    • Present address: Division of Immunoregulation, National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA London, UK.

Received 15 July 2009 ,Revised 15 September 2009 ,Accepted 26 September 2009.

References 

  1. Dustin LB, Rice CM. Flying under the radar: the immunobiology of hepatitis C. Annu Rev Immunol. 2007;25:71–99
  2. Bigger CB, Brasky KM, Lanford RE. DNA microarray analysis of chimpanzee liver during acute resolving hepatitis C virus infection. J Virol. 2001;75:7059–7066
  3. Bigger CB, Guerra B, Brasky KM, Hubbard G, Beard MR, Luxon BA, et al. Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees. J Virol. 2004;78:13779–13792
  4. Su AI, Pezacki JP, Wodicka L, Brideau AD, Supekova L, Thimme R, et al. Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci USA. 2002;99:15669–15674
  5. Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC, Ikeda M, et al. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci USA. 2005;102:2992–2997
  6. Foy E, Li K, Wang C, Sumpter R, Ikeda M, Lemon SM, et al. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science. 2003;300:1145–1148
  7. Taylor DR, Shi ST, Romano PR, Barber GN, Lai MM. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science. 1999;285:107–110
  8. Gale M, Blakely CM, Kwieciszewski B, Tan SL, Dossett M, Tang NM, et al. Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. Mol Cell Biol. 1998;18:5208–5218
  9. Geiss GK, Carter VS, He Y, Kwieciszewski BK, Holzman T, Korth MJ, et al. Gene expression profiling of the cellular transcriptional network regulated by alpha/beta interferon and its partial attenuation by the hepatitis C virus nonstructural 5A protein. J Virol. 2003;77:6367–6375
  10. Polyak SJ, Khabar KS, Paschal DM, Ezelle HJ, Duverlie G, Barber GN, et al. Hepatitis C virus nonstructural 5A protein induces interleukin-8, leading to partial inhibition of the interferon-induced antiviral response. J Virol. 2001;75:6095–6106
  11. Khabar KS, Al-Zoghaibi F, Al-Ahdal MN, Murayama T, Dhalla M, Mukaida N, et al. The alpha chemokine, interleukin 8, inhibits the antiviral action of interferon alpha. J Exp Med. 1997;186:1077–1085
  12. Koo BC, McPoland P, Wagoner JP, Kane OJ, Lohmann V, Polyak SJ. Relationships between hepatitis C virus replication and CXCL-8 production in vitro. J Virol. 2006;80:7885–7893
  13. Polyak SJ, Khabar KS, Rezeiq M, Gretch DR. Elevated levels of interleukin-8 in serum are associated with hepatitis C virus infection and resistance to interferon therapy. J Virol. 2001;75:6209–6211
  14. Newman KC, Riley EM. Whatever turns you on: accessory-cell-dependent activation of NK cells by pathogens. Nat Rev Immunol. 2007;7:279–291
  15. Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science. 2004;305:872–874
  16. Crotta S, Stilla A, Wack A, D’Andrea A, Nuti S, D’Oro U, et al. Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus envelope protein. J Exp Med. 2002;195:35–41
  17. Tseng CT, Klimpel GR. Binding of the hepatitis C virus envelope protein E2 to CD81 inhibits natural killer cell functions. J Exp Med. 2002;195:43–49
  18. Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, et al. Complete replication of hepatitis C virus in cell culture. Science. 2005;309:623–626
  19. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, et al. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med. 2005;11:791–796
  20. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR, et al. Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci USA. 2005;102:9294–9299
  21. Yoon JC, Shiina M, Ahlenstiel G, Rehermann B. Natural killer cell function is intact after direct exposure to infectious hepatitis C virions. Hepatology. 2009;49:12–21
  22. Frese M, Schwarzle V, Barth K, Krieger N, Lohmann V, Mihm S, et al. Interferon-gamma inhibits replication of subgenomic and genomic hepatitis C virus RNAs. Hepatology. 2002;35:694–703
  23. Rosa D, Saletti G, De Gregorio E, Zorat F, Comar C, D’Oro U, et al. Activation of naïve B lymphocytes via CD81, a pathogenetic mechanism for HCV-associated B-lymphocyte disorders. Proc Natl Acad Sci USA. 2005;102:18544–18549
  24. Heile JM, Fong YL, Rosa D, Berger K, Saletti G, Campagnoli S, et al. Evaluation of hepatitis C virus glycoprotein E2 for vaccine design: an endoplasmic reticulum-retained recombinant protein is superior to secreted recombinant protein and DNA-based vaccine candidates. J Virol. 2000;74:6885–6892
  25. Perussia B, Ramoni C, Anegon I, Cuturi MC, Faust J, Trinchieri G. Preferential proliferation of natural killer cells among peripheral blood mononuclear cells cocultured with B lymphoblastoid cell lines. Nat Immun Cell Growth Regul. 1987;6:171–188
  26. Wack A, Soldaini E, Tseng C, Nuti S, Klimpel G, Abrignani S. Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells. Eur J Immunol. 2001;31:166–175
  27. Zhu Q, Oei Y, Mendel DB, Garrett EN, Patawaran MB, Hollenbach PW, et al. Novel robust hepatitis C virus mouse efficacy model. Antimicrob Agents Chemother. 2006;50:3260–3268
  28. Lohmann V, Korner F, Koch J, Herian U, Theilmann L, Bartenschlager R. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science. 1999;285:110–113
  29. Marukian S, Jones CT, Andrus L, Evans MJ, Ritola KD, Charles ED, et al. Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells. Hepatology. 2008;48:1843–1850
  30. Orange JS, Biron CA. An absolute and restricted requirement for IL-12 in natural killer cell IFN-gamma production and antiviral defense. Studies of natural killer and T cell responses in contrasting viral infections. J Immunol. 1996;156:1138–1142
  31. Monteiro JM, Harvey C, Trinchieri G. Role of interleukin-12 in primary influenza virus infection. J Virol. 1998;72:4825–4831
  32. Krug A, French AR, Barchet W, Fischer JA, Dzionek A, Pingel JT, et al. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity. 2004;21:107–119
  33. Ludwig IS, Lekkerkerker AN, Depla E, Bosman F, Musters RJ, Depraetere S, et al. Hepatitis C virus targets DC-SIGN and L-SIGN to escape lysosomal degradation. J Virol. 2004;78:8322–8332
  34. Crotta S, Ronconi V, Ulivieri C, Baldari CT, Valiante NM, Abrignani S, et al. Cytoskeleton rearrangement induced by tetraspanin engagement modulates the activation of T and NK cells. Eur J Immunol. 2006;36:919–929

PII: S0168-8278(09)00729-6

doi: 10.1016/j.jhep.2009.11.003

Journal of Hepatology
Volume 52, Issue 2 , Pages 183-190 , February 2010