1887

Journal of General Virology

Volume 97, Issue 2

Contribution of the interaction between the rabies virus P protein and I-kappa B kinase to the inhibition of type I IFN induction signalling Free

Abstract

The P protein of rabies virus (RABV) is known to interfere with the phosphorylation of the host IFN regulatory factor 3 (IRF-3) and to consequently inhibit type I IFN induction. Previous studies, however, have only tested P proteins from laboratory-adapted fixed virus strains, and to the best of our knowledge there is no report about the effect of P proteins from street RABV strains or other lyssaviruses on the IRF-3-mediated type I IFN induction system. In this study, we evaluated the inhibitory effect of P proteins from several RABV strains, including fixed and street virus strains and other lyssaviruses (Lagos bat, Mokola and Duvenhage viruses), on IRF-3 signalling. All P proteins tested inhibited retinoic acid-inducible gene-1 (RIG-I)- and TANK binding kinase 1 (TBK1)-mediated IRF-3-dependent IFN-β promoter activities. On the other hand, the P proteins from the RABV street strains 1088 and HCM-9, but not from fixed strains Nishigahara (Ni) and CVS-11 and other lyssaviruses tested, significantly inhibited I-kappa B kinase ϵ (IKKϵ)-inducible IRF-3-dependent IFN-β promoter activity. Importantly, we revealed that the P proteins from the 1088 and HCM-9 strains, but not from the remaining viruses, interacted with IKKϵ. By using expression plasmids encoding chimeric P proteins from the 1088 strain and Ni strain, we found that the C-terminal region of the P protein is important for the interaction with IKKϵ. These findings suggest that the P protein of RABV street strains may contribute to efficient evasion of host innate immunity.

  • Received:
  • Accepted:
  • Published Online:
© 2015 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000362
2016-02-01
2019-12-11
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/2/316.html?itemId=/content/journal/jgv/10.1099/jgv.0.000362&mimeType=html&fmt=ahah

References

  1. Adli M., Baldwin A. S.. 2006; IKK-i/IKKepsilon controls constitutive, cancer cell-associated NF-kappaB activity via regulation of Ser-536 p65/RelA phosphorylation. J Biol Chem281:26976–26984 [CrossRef][PubMed]
     [Google Scholar]
  2. Akira S., Uematsu S., Takeuchi O.. 2006; Pathogen recognition and innate immunity. Cell124:783–801 [CrossRef][PubMed]
     [Google Scholar]
  3. Badrane H., Bahloul C., Perrin P., Tordo N.. 2001; Evidence of two Lyssavirus phylogroups with distinct pathogenicity and immunogenicity. J Virol75:3268–3276 [CrossRef][PubMed]
     [Google Scholar]
  4. Banyard A. C., Evans J. S., Luo T. R., Fooks A. R.. 2014; Lyssaviruses and bats: emergence and zoonotic threat. Viruses6:2974–2990 [CrossRef][PubMed]
     [Google Scholar]
  5. Blondel D., Maarifi G., Nisole S., Chelbi-Alix M. K.. 2015; Resistance to Rhabdoviridae infection and subversion of antiviral responses. Viruses7:3675–3702 [CrossRef][PubMed]
     [Google Scholar]
  6. Bonjardim C. A.. 2005; Interferons (IFNs) are key cytokines in both innate and adaptive antiviral immune responses–and viruses counteract IFN action. Microbes Infect7:569–578 [CrossRef][PubMed]
     [Google Scholar]
  7. Brzózka K., Finke S., Conzelmann K. K.. 2005; Identification of the rabies virus alpha/beta interferon antagonist: phosphoprotein P interferes with phosphorylation of interferon regulatory factor 3. J Virol79:7673–7681 [CrossRef][PubMed]
     [Google Scholar]
  8. Brzózka K., Finke S., Conzelmann K. K.. 2006; Inhibition of interferon signaling by rabies virus phosphoprotein P: activation-dependent binding of STAT1 and STAT2. J Virol80:2675–2683 [CrossRef][PubMed]
     [Google Scholar]
  9. Chenik M., Chebli K., Gaudin Y., Blondel D.. 1994; In vivo interaction of rabies virus phosphoprotein (P) and nucleoprotein (N): existence of two N-binding sites on P protein. J Gen Virol75:2889–2896 [CrossRef][PubMed]
     [Google Scholar]
  10. Chenik M., Schnell M., Conzelmann K. K., Blondel D.. 1998; Mapping the interacting domains between the rabies virus polymerase and phosphoprotein. J Virol72:1925–1930[PubMed]
     [Google Scholar]
  11. Dietzschold B., Li J., Faber M., Schnell M.. 2008; Concepts in the pathogenesis of rabies. Future Virol3:481–490 [CrossRef][PubMed]
     [Google Scholar]
  12. Finke S., Conzelmann K. K.. 2005; Replication strategies of rabies virus. Virus Res111:120–131 [CrossRef][PubMed]
     [Google Scholar]
  13. 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; IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol4:491–496 [CrossRef][PubMed]
     [Google Scholar]
  14. Fouquet B., Nikolic J., Larrous F., Bourhy H., Wirblich C., Lagaudrière-Gesbert C., Blondel D.. 2015; Focal adhesion kinase is involved in rabies virus infection through its interaction with viral phosphoprotein P. J Virol89:1640–1651 [CrossRef][PubMed]
     [Google Scholar]
  15. 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. Science314:994–997 [CrossRef][PubMed]
     [Google Scholar]
  16. Ishikawa Y., Samejima T., Nunoya T., Motohashi T., Nomura Y.. 1989; Biological properties of the cell culture-adapted RC-HL strain of rabies virus as a candidate strain for an inactivated vaccine. J Jpn Vet Med Assoc42:637–643 [CrossRef]
     [Google Scholar]
  17. Ito N., Moseley G. W., Blondel D., Shimizu K., Rowe C. L., Ito Y., Masatani T., Nakagawa K., Jans D. A., Sugiyama M.. 2010; Role of interferon antagonist activity of rabies virus phosphoprotein in viral pathogenicity. J Virol84:6699–6710 [CrossRef][PubMed]
     [Google Scholar]
  18. 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. Nature441:101–105 [CrossRef][PubMed]
     [Google Scholar]
  19. Kobasa D., Rodgers M. E., Wells K., Kawaoka Y.. 1997; Neuraminidase hemadsorption activity, conserved in avian influenza A viruses, does not influence viral replication in ducks. J Virol71:6706–6713[PubMed]
     [Google Scholar]
  20. Koraka P., Martina B. E., Roose J. M., van Thiel P. P., van Amerongen G., Kuiken T., Osterhaus A. D.. 2012; In vitro and in vivo isolation and characterization of Duvenhage virus. PLoS Pathog8:e1002682 [CrossRef][PubMed]
     [Google Scholar]
  21. Lépine P.. 1938; On the evolution of fixed strains of rabies virus. J Hyg (Lond)38:180–184 [CrossRef][PubMed]
     [Google Scholar]
  22. Lieu K. G., Brice A., Wiltzer L., Hirst B., Jans D. A., Blondel D., Moseley G. W.. 2013; The rabies virus interferon antagonist P protein interacts with activated STAT3 and inhibits Gp130 receptor signaling. J Virol87:8261–8265 [CrossRef][PubMed]
     [Google Scholar]
  23. Masatani T., Ito N., Shimizu K., Ito Y., Nakagawa K., Sawaki Y., Koyama H., Sugiyama M.. 2010; Rabies virus nucleoprotein functions to evade activation of the RIG-I-mediated antiviral response. J Virol84:4002–4012 [CrossRef][PubMed]
     [Google Scholar]
  24. Mifune K., Makino Y., Mannen K.. 1979; Susceptibility of various cell lines to rabies virus. J Trop Med Hyg7:201–208 [CrossRef]
     [Google Scholar]
  25. Ng S. L., Friedman B. A., Schmid S., Gertz J., Myers R. M., Tenoever B. R., Maniatis T.. 2011; IκB kinase epsilon (IKKϵ) regulates the balance between type I and type II interferon responses. Proc Natl Acad Sci U S A108:21170–21175 [CrossRef][PubMed]
     [Google Scholar]
  26. Niu X., Tang L., Tseggai T., Guo Y., Fu Z. F.. 2013; Wild-type rabies virus phosphoprotein is associated with viral sensitivity to type I interferon treatment. Arch Virol158:2297–2305 [CrossRef][PubMed]
     [Google Scholar]
  27. Nolden T., Banyard A. C., Finke S., Fooks A. R., Hanke D., Höper D., Horton D. L., Mettenleiter T. C., Müller T., other authors. 2014; Comparative studies on the genetic, antigenic and pathogenic characteristics of Bokeloh bat lyssavirus. J Gen Virol95:1647–1653 [CrossRef][PubMed]
     [Google Scholar]
  28. Oksayan S., Nikolic J., David C. T., Blondel D., Jans D. A., Moseley G. W.. 2015; Identification of a role for nucleolin in rabies virus infection. J Virol89:1939–1943 [CrossRef][PubMed]
     [Google Scholar]
  29. Pham A. M., Tenoever B. R.. 2010; The IKK kinases: operators of antiviral signaling. Viruses2:55–72 [CrossRef][PubMed]
     [Google Scholar]
  30. Randall R. E., Goodbourn S.. 2008; Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol89:1–47 [CrossRef][PubMed]
     [Google Scholar]
  31. Rieder M., Brzózka K., Pfaller C. K., Cox J. H., Stitz L., Conzelmann K. K.. 2011; Genetic dissection of interferon-antagonistic functions of rabies virus phosphoprotein: inhibition of interferon regulatory factor 3 activation is important for pathogenicity. J Virol85:842–852 [CrossRef][PubMed]
     [Google Scholar]
  32. Schnell M. J., McGettigan J. P., Wirblich C., Papaneri A.. 2010; The cell biology of rabies virus: using stealth to reach the brain. Nat Rev Microbiol8:51–61[PubMed]
     [Google Scholar]
  33. 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. Science300:1148–1151 [CrossRef][PubMed]
     [Google Scholar]
  34. Shimada T., Kawai T., Takeda K., Matsumoto M., Inoue J., Tatsumi Y., Kanamaru A., Akira S.. 1999; IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases. Int Immunol11:1357–1362 [CrossRef][PubMed]
     [Google Scholar]
  35. Tenoever B. R., Ng S. L., Chua M. A., McWhirter S. M., García-Sastre A., Maniatis T.. 2007; Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity. Science315:1274–1278 [CrossRef][PubMed]
     [Google Scholar]
  36. van Boxel-Dezaire A. H., Rani M. R., Stark G. R.. 2006; Complex modulation of cell type-specific signaling in response to type I interferons. Immunity25:361–372 [CrossRef][PubMed]
     [Google Scholar]
  37. Vidy A., Chelbi-Alix M., Blondel D.. 2005; Rabies virus P protein interacts with STAT1 and inhibits interferon signal transduction pathways. J Virol79:14411–14420 [CrossRef][PubMed]
     [Google Scholar]
  38. Vidy A., El Bougrini J., Chelbi-Alix M. K., Blondel D.. 2007; The nucleocytoplasmic rabies virus P protein counteracts interferon signaling by inhibiting both nuclear accumulation and DNA binding of STAT1. J Virol81:4255–4263 [CrossRef][PubMed]
     [Google Scholar]
  39. Wiltzer L., Larrous F., Oksayan S., Ito N., Marsh G. A., Wang L. F., Blondel D., Bourhy H., Jans D. A., Moseley G. W.. 2012; Conservation of a unique mechanism of immune evasion across the Lyssavirus genus. J Virol86:10194–10199 [CrossRef][PubMed]
     [Google Scholar]
  40. Wiltzer L., Okada K., Yamaoka S., Larrous F., Kuusisto H. V., Sugiyama M., Blondel D., Bourhy H., Jans D. A., other authors. 2014; Interaction of rabies virus P-protein with STAT proteins is critical to lethal rabies disease. J Infect Dis209:1744–1753 [CrossRef][PubMed]
     [Google Scholar]
  41. Yamagata J., Ahmed K., Khawplod P., Mannen K., Xuyen D. K., Loi H. H., Dung N. V., Nishizono A.. 2007; Molecular epidemiology of rabies in Vietnam. Microbiol Immunol51:833–840 [CrossRef][PubMed]
     [Google Scholar]
  42. Yoneyama M., Suhara W., Fukuhara Y., Sato M., Ozato K., Fujita T.. 1996; Autocrine amplification of type I interferon gene expression mediated by interferon stimulated gene factor 3 (ISGF3). J Biochem120:160–169 [CrossRef][PubMed]
     [Google Scholar]
  43. Yoneyama M., Kikuchi M., Matsumoto K., Imaizumi T., Miyagishi M., Taira K., Foy E., Loo Y. M., Gale M. Jr., other authors. 2005; Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol175:2851–2858 [CrossRef][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000362
Loading
Contribution of the interaction between the rabies virus P protein and I-kappa B kinase ϵ to the inhibition of type I IFN induction signalling
J. Gen. Virol. 97, 316 (2016); https://doi.org/10.1099/jgv.0.000362
/content/journal/jgv/10.1099/jgv.0.000362
/content/journal/jgv/10.1099/jgv.0.000362
Loading

Data & Media loading...

Supplements

Supplementary Data

PDF

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