1887

Abstract

Hepatitis A virus (HAV) antagonizes the innate immune response by inhibition of retinoic acid-inducible gene I-mediated and melanoma differentiation-associated gene 5-mediated beta interferon (IFN-) gene expression. This study showed that this is due to an interaction of HAV with mitochondrial antiviral signalling protein (MAVS)-dependent signalling, in which the viral non-structural protein 2B and the protein intermediate 3ABC recently suggested in this context seem to be involved, cooperatively affecting the activities of MAVS and the kinases TANK-binding kinase 1 (TBK1) and the inhibitor of NF-B kinase ϵ (IKKϵ). In consequence, interferon regulatory factor 3 (IRF-3) is not activated. As IRF-3 is necessary for IFN- transcription, inhibition of this factor results in efficient suppression of IFN- synthesis. This ability might be of vital importance for HAV, which is an exceptionally slow growing virus sensitive to IFN-, as it allows the virus to establish infection and maintain virus replication for a longer period of time.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83521-0
2008-07-01
2020-01-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/7/1593.html?itemId=/content/journal/jgv/10.1099/vir.0.83521-0&mimeType=html&fmt=ahah

References

  1. Brack, K., Frings, W., Dotzauer, A. & Vallbracht, A. ( 1998; ). A cytopathogenic, apoptosis-inducing variant of hepatitis A virus. J Virol 72, 3370–3376.
    [Google Scholar]
  2. Brack, K., Berk, I., Magulski, T., Lederer, J., Dotzauer, A. & Vallbracht, A. ( 2002; ). Hepatitis A virus inhibits cellular antiviral defense mechanisms induced by double-stranded RNA. J Virol 76, 11920–11930.[CrossRef]
    [Google Scholar]
  3. Chan, D. C. ( 2006; ). Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol 22, 79–99.[CrossRef]
    [Google Scholar]
  4. Chariot, A., Leonardi, A., Müller, J., Bonif, M., Brown, K. & Siebenlist, U. ( 2002; ). Association of the adaptor TANK with the IκB kinase (IKK) regulator NEMO connects IKK complexes with IKKϵ and TBK1 kinases. J Biol Chem 277, 37029–37036.[CrossRef]
    [Google Scholar]
  5. Chen, H. & Chan, D. C. ( 2005; ). Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14, R283–R289.[CrossRef]
    [Google Scholar]
  6. Chow, E. K., Castrillo, A., Shahangian, A., Pei, L., O'Connell, R. M., Modlin, R. L., Tontonoz, P. & Cheng, G. ( 2006; ). A role for IRF-3-dependent RXRα repression in hepatotoxicity associated with viral infections. J Exp Med 203, 2589–2602.[CrossRef]
    [Google Scholar]
  7. Cohen, J. I., Rosenblum, B., Ticehurst, J. T., Daemer, R. J., Feinstone, S. M. & Purcell, R. H. ( 1987; ). Complete nucleotide sequence of an attenuated hepatitis A virus: comparison with wild-type virus. Proc Natl Acad Sci U S A 84, 2497–2501.[CrossRef]
    [Google Scholar]
  8. Doedens, J. R. & Kirkegaard, K. ( 1995; ). Inhibition of cellular protein secretion by poliovirus proteins 2B and 3A. EMBO J 14, 894–907.
    [Google Scholar]
  9. Dotzauer, A., Feinstone, S. M. & Kaplan, G. ( 1994; ). Susceptibility of nonprimate cell lines to hepatitis A virus infection. J Virol 68, 6064–6068.
    [Google Scholar]
  10. Dotzauer, A., Gebhardt, U., Bieback, K., Göttke, U., Kracke, A., Mages, J., Lemon, S. M. & Vallbracht, A. ( 2000; ). Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor. J Virol 74, 10950–10957.[CrossRef]
    [Google Scholar]
  11. Ehrhardt, C., Kardinal, C., Wurzer, W. J., Wolff, T., von Eichel-Streiber, C., Pleschka, S., Planz, O. & Ludwig, S. ( 2004; ). Rac1 and PAK1 are upstream of IKK-ϵ and TBK-1 in the viral activation of interferon regulatory factor-3. FEBS Lett 567, 230–238.[CrossRef]
    [Google Scholar]
  12. Emerson, S. U., McRill, C., Rosenblum, B., Feinstone, S. M. & Purcell, R. H. ( 1991; ). Mutations responsible for adaptation of hepatitis A virus to efficient growth in cell culture. J Virol 65, 4882–4886.
    [Google Scholar]
  13. Emerson, S. U., Huang, Y. K., McRill, C., Lewis, M. & Purcell, R. H. ( 1992; ). Mutations in both the 2B and 2C genes of hepatitis A virus are involved in adaptation to growth in cell culture. J Virol 66, 650–654.
    [Google Scholar]
  14. Emerson, S. U., Huang, Y. K. & Purcell, R. H. ( 1993; ). 2B and 2C mutations are essential but mutations throughout the genome of HAV contribute to adaptation to cell culture. Virology 194, 475–480.[CrossRef]
    [Google Scholar]
  15. Fensterl, V., Grotheer, D., Berk, I., Schlemminger, S., Vallbracht, A. & Dotzauer, A. ( 2005; ). Hepatitis A virus suppresses RIG-I-mediated IRF-3 activation to block induction of beta interferon. J Virol 79, 10968–10977.[CrossRef]
    [Google Scholar]
  16. Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S.-M. & Maniatis, T. ( 2003; ). IKKϵ and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4, 491–496.
    [Google Scholar]
  17. Fleischer, B., Fleischer, S., Maier, K., Wiedmann, K. H., Sacher, M., Thaler, H. & Vallbracht, A. ( 1990; ). Clonal analysis of infiltrating T lymphocytes in liver tissue in viral hepatitis A. Immunology 69, 14–19.
    [Google Scholar]
  18. Gauss-Müller, V. & Deinhardt, F. ( 1984; ). Effect of hepatitis A virus infection on cell metabolism in vitro. Proc Soc Exp Biol Med 175, 10–15.[CrossRef]
    [Google Scholar]
  19. Gitlin, L., Barchet, W., Gilfillan, S., Cella, M., Beutler, B., Flavell, R. A., Diamond, M. S. & Colonna, M. ( 2006; ). Essential role of mda-5 in type I IFN responses to polyriboinosinic : polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci U S A 103, 8459–8464.[CrossRef]
    [Google Scholar]
  20. Gosert, R., Dollenmaier, G. & Weitz, M. ( 1997; ). Identification of active-site residues in protease 3C of hepatitis A virus by site-directed mutagenesis. J Virol 71, 3062–3068.
    [Google Scholar]
  21. Gosert, R., Egger, D. & Bienz, K. ( 2000; ). A cytopathic and a cell culture adapted hepatitis A virus strain differ in cell killing but not in intracellular membrane rearrangements. Virology 266, 157–169.[CrossRef]
    [Google Scholar]
  22. Gust, I. D. & Feinstone, S. M. ( 1988; ). Hepatitis A. Boca Raton, FL: CRC Press.
  23. Hemmi, H., Takeuchi, O., Sato, S., Yamamoto, M., Kaisho, T., Sanjo, H., Kawai, T., Hoshino, K., Takeda, K. & Akira, S. ( 2004; ). The roles of two IκB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J Exp Med 199, 1641–1650.[CrossRef]
    [Google Scholar]
  24. Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.-K. & other authors ( 2006; ). 5′-Triphosphate RNA is the ligand for RIG-I. Science 314, 994–997.[CrossRef]
    [Google Scholar]
  25. Jecht, M., Probst, C. & Gauss-Müller, V. ( 1998; ). Membrane permeability induced by hepatitis A virus proteins 2B and 2BC and proteolytic processing of HAV 2BC. Virology 252, 218–227.[CrossRef]
    [Google Scholar]
  26. Kärber, G. ( 1931; ). Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche. Arch Exp Pathol Pharmakol 162, 480–483 in German.[CrossRef]
    [Google Scholar]
  27. Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T. & other authors ( 2006; ). Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441, 101–105.[CrossRef]
    [Google Scholar]
  28. Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O. & Akira, S. ( 2005; ). IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 6, 981–988.[CrossRef]
    [Google Scholar]
  29. Lama, J. & Carrasco, L. ( 1992; ). Expression of poliovirus nonstructural proteins in Escherichia coli cells. Modification of membrane permeability by 2B and 3A. J Biol Chem 267, 15932–15937.
    [Google Scholar]
  30. Lin, R., Heylbroeck, C., Pitha, P. M. & Hiscott, J. ( 1998; ). Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Mol Cell Biol 18, 2986–2996.
    [Google Scholar]
  31. Maier, K., Gabriel, P., Koscielniak, E., Stierhof, Y.-D., Wiedmann, K. H., Flehmig, B. & Vallbracht, A. ( 1988; ). Human gamma interferon production by cytotoxic T lymphocytes sensitized during hepatitis A virus infection. J Virol 62, 3756–3763.
    [Google Scholar]
  32. Martin, A., Bénichou, D., Chao, S.-F., Cohen, L. M. & Lemon, S. M. ( 1999; ). Maturation of the hepatitis A virus capsid protein VP1 is not dependent on processing by the 3Cpro proteinase. J Virol 73, 6220–6227.
    [Google Scholar]
  33. McWhirter, S. M., Fitzgerald, K. A., Rosains, J., Rowe, D. C., Golenbock, D. T. & Maniatis, T. ( 2004; ). IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. Proc Natl Acad Sci U S A 101, 233–238.[CrossRef]
    [Google Scholar]
  34. Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R. & Tschopp, J. ( 2005; ). Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437, 1167–1172.[CrossRef]
    [Google Scholar]
  35. Oshiumi, H., Matsumoto, M., Funami, K., Akazawa, T. & Seya, T. ( 2003; ). TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-β induction. Nat Immunol 4, 161–167.[CrossRef]
    [Google Scholar]
  36. Pichlmair, A., Schulz, O., Tan, C. P., Näslund, T. I., Liljeström, P., Weber, F. & Reis e Sousa, C. ( 2006; ). RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314, 997–1001.[CrossRef]
    [Google Scholar]
  37. Probst, C., Jecht, M. & Gauss-Müller, V. ( 1998; ). Processing of proteinase precursors and their effect on hepatitis A virus particle formation. J Virol 72, 8013–8020.
    [Google Scholar]
  38. Sato, S., Sugiyama, M., Yamamoto, M., Watanabe, Y., Kawai, T., Takeda, K. & Akira, S. ( 2003; ). Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-κB and IFN-regulatory factor-3, in the Toll-like receptor signaling. J Immunol 171, 4304–4310.[CrossRef]
    [Google Scholar]
  39. Schultheiss, T., Sommergruber, W., Kusov, Y. & Gauss-Müller, V. ( 1995; ). Cleavage specificity of purified recombinant hepatitis A virus 3C proteinase on natural substrates. J Virol 69, 1727–1733.
    [Google Scholar]
  40. Seth, R. B., Sun, L., Ea, C. K. & Chen, Z. J. ( 2005; ). Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF3. Cell 122, 669–682.[CrossRef]
    [Google Scholar]
  41. Sharma, S., tenOever, B. R., Grandvaux, N., Zhou, G.-P., Lin, R. & Hiscott, J. ( 2003; ). Triggering the interferon antiviral response through an IKK-related pathway. Science 300, 1148–1151.[CrossRef]
    [Google Scholar]
  42. Tasaka, M., Sakamoto, N., Itakura, Y., Nakagawa, M., Itsui, Y., Sekine-Osajima, Y., Nishimura-Sakurai, Y., Chen, C.-H., Yoneyama, N. & other authors ( 2007; ). Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response. J Gen Virol 88, 3323–3333.[CrossRef]
    [Google Scholar]
  43. Teterina, N. L., Bienz, K., Egger, D., Gorbalenya, A. E. & Ehrenfeld, E. ( 1997; ). Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC. Virology 237, 66–77.[CrossRef]
    [Google Scholar]
  44. Thanos, D. & Maniatis, T. ( 1995; ). Virus induction of human IFNβ gene expression requires the assembly of an enhanceosome. Cell 83, 1091–1100.[CrossRef]
    [Google Scholar]
  45. Tojima, Y., Fujimoto, A., Delhase, M., Chen, Y., Hatakeyama, S., Nakayama, K.-I., Kaneko, Y., Nimura, Y., Motoyama, N. & other authors ( 2000; ). NAK is an IκB kinase-activating kinase. Nature 404, 778–782.[CrossRef]
    [Google Scholar]
  46. Vallbracht, A. & Flehmig, B. ( 1985a; ). Elimination of a persistent hepatitis A infection in cell cultures by interferon. In The Biology of the Interferon System 1984, pp. 339–345. Edited by H. Kirchner & H. Schellekens. Amsterdam, The Netherlands: Elsevier Science Publishers B.V.
  47. Vallbracht, A., Hofman, L., Wurster, K. G. & Flehmig, B. ( 1984; ). Persistent infection of human fibroblasts by hepatitis A virus. J Gen Virol 65, 609–615.[CrossRef]
    [Google Scholar]
  48. Vallbracht, A., Gabriel, P., Zahn, J. & Flehmig, B. ( 1985b; ). Hepatitis A virus infection and the interferon system. J Infect Dis 152, 211–213.[CrossRef]
    [Google Scholar]
  49. Vallbracht, A., Maier, K., Stierhof, Y.-D., Wiedmann, K. H., Flehmig, B. & Fleischer, B. ( 1989; ). Liver-derived cytotoxic T cells in hepatitis A virus infection. J Infect Dis 160, 209–217.[CrossRef]
    [Google Scholar]
  50. van Kuppeveld, F. J. M., Hoenderop, J. G. J., Smeets, R. L. L., Willems, P. H. G. M., Dijkman, H. B. P. M., Galama, J. M. D. & Melchers, W. J. G. ( 1997; ). Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release. EMBO J 16, 3519–3532.[CrossRef]
    [Google Scholar]
  51. Xu, L.-G., Wang, Y.-Y., Han, K.-J., Li, L.-Y., Zhai, Z. & Shu, H.-B. ( 2005; ). VISA is an adapter protein required for virus-triggered IFN-β signaling. Mol Cell 19, 727–740.[CrossRef]
    [Google Scholar]
  52. Yamamoto, M., Sato, S., Mori, K., Hoshino, K., Takeuchi, O., Takeda, K. & Akira, S. ( 2002; ). A novel toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-β promoter in the Toll-like receptor signaling. J Immunol 169, 6668–6672.[CrossRef]
    [Google Scholar]
  53. Yang, H., Ma, G., Lin, C. H., Orr, M. & Wathelet, M. G. ( 2004; ). Mechanism for transcriptional synergy between interferon regulatory factor (IRF)-3 and IRF-7 in activation of the interferon-β gene promoter. Eur J Biochem 271, 3693–3703.[CrossRef]
    [Google Scholar]
  54. Yang, Y., Liang, Y., Qu, L., Chen, Z., Yi, M., Li, K. & Lemon, S. M. ( 2007; ). Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor. Proc Natl Acad Sci U S A 104, 7253–7258.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83521-0
Loading
/content/journal/jgv/10.1099/vir.0.83521-0
Loading

Data & Media loading...

Most cited articles

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