1887

Abstract

The innate antiviral response is initiated by pattern recognition receptors, which recognize viral pathogen-associated molecular patterns. Here we show that retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) in cooperation with Toll-like receptor (TLR) 9 is required for expression of type I interferons (IFNs) after infection with herpes simplex virus (HSV). Our work also identified RNase L as a critical component in IFN induction. Moreover, we found that TLR9 and RLRs activate distinct, as well as overlapping, intracellular signalling pathways. Thus, RLRs are important for recognition of HSV infection, and cooperate with the Toll pathway to induce an antiviral response.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.005389-0
2009-01-01
2019-11-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/1/74.html?itemId=/content/journal/jgv/10.1099/vir.0.005389-0&mimeType=html&fmt=ahah

References

  1. Alexopoulou, L., Holt, A. C., Medzhitov, R. & Flavell, R. A. ( 2001; ). Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732–738.[CrossRef]
    [Google Scholar]
  2. Ank, N., West, H., Bartholdy, C., Eriksson, K., Thomsen, A. R. & Paludan, S. R. ( 2006; ). Lambda interferon (IFN-λ), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 80, 4501–4509.[CrossRef]
    [Google Scholar]
  3. Aravalli, R. N., Hu, S., Rowen, T. N., Palmquist, J. M. & Lokensgard, J. R. ( 2005; ). Cutting edge: TLR2-mediated proinflammatory cytokine and chemokine production by microglial cells in response to herpes simplex virus. J Immunol 175, 4189–4193.[CrossRef]
    [Google Scholar]
  4. Beutler, B. ( 2004; ). Inferences, questions and possibilities in Toll-like receptor signalling. Nature 430, 257–263.[CrossRef]
    [Google Scholar]
  5. Biron, C. A., Byron, K. S. & Sullivan, J. L. ( 1989; ). Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med 320, 1731–1735.[CrossRef]
    [Google Scholar]
  6. Boehme, K. W., Guerrero, M. & Compton, T. ( 2006; ). Human cytomegalovirus envelope glycoproteins B and H are necessary for TLR2 activation in permissive cells. J Immunol 177, 7094–7102.[CrossRef]
    [Google Scholar]
  7. Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S. & Reis e Sousa, C. ( 2004; ). Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303, 1529–1531.[CrossRef]
    [Google Scholar]
  8. Dupuis, S., Jouanguy, E., Al Hajjar, S., Fieschi, C., Al Mohsen, I. Z., Al Jumaah, S., Yang, K., Chapgier, A., Eidenschenk, C. & other authors ( 2003; ). Impaired response to interferon-α/β and lethal viral disease in human STAT1 deficiency. Nat Genet 33, 388–391.[CrossRef]
    [Google Scholar]
  9. Hochrein, H., Schlatter, B., O'Keeffe, M., Wagner, C., Schmitz, F., Schiemann, M., Bauer, S., Suter, M. & Wagner, H. ( 2004; ). Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways. Proc Natl Acad Sci U S A 101, 11416–11421.[CrossRef]
    [Google Scholar]
  10. Hornung, V., Ellegast, J., Kim, S., Brzozka, 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]
  11. 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]
  12. Kawai, T. & Akira, S. ( 2006; ). Innate immune recognition of viral infection. Nat Immunol 7, 131–137.
    [Google Scholar]
  13. Krug, A., Luker, G. D., Barchet, W., Leib, D. A., Akira, S. & Colonna, M. ( 2004; ). Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 103, 1433–1437.
    [Google Scholar]
  14. Kurt-Jones, E. A., Popova, L., Kwinn, L., Haynes, L. M., Jones, L. P., Tripp, R. A., Walsh, E. E., Freeman, M. W., Golenbock, D. T. & other authors ( 2000; ). Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol 1, 398–401.[CrossRef]
    [Google Scholar]
  15. Kurt-Jones, E. A., Chan, M., Zhou, S., Wang, J., Reed, G., Bronson, R., Arnold, M. M., Knipe, D. M. & Finberg, R. W. ( 2004; ). Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci U S A 101, 1315–1320.[CrossRef]
    [Google Scholar]
  16. Kurt-Jones, E. A., Belko, J., Yu, C., Newburger, P. E., Wang, J., Chan, M., Knipe, D. M. & Finberg, R. W. ( 2005; ). The role of toll-like receptors in herpes simplex infection in neonates. J Infect Dis 191, 746–748.[CrossRef]
    [Google Scholar]
  17. Le Goffic, R., Pothlichet, J., Vitour, D., Fujita, T., Meurs, E., Chignard, M. & Si-Tahar, M. ( 2007; ). Cutting edge: influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells. J Immunol 178, 3368–3372.[CrossRef]
    [Google Scholar]
  18. Leib, D. A., Harrison, T. E., Laslo, K. M., Machalek, M. A., Moorman, N. J. & Virgin, H. W. ( 1999; ). Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. J Exp Med 189, 663–672.[CrossRef]
    [Google Scholar]
  19. Liu, P., Jamaluddin, M., Li, K., Garofalo, R. P., Casola, A. & Brasier, A. R. ( 2007; ). Retinoic acid-inducible gene I mediates early antiviral response and Toll-like receptor 3 expression in respiratory syncytial virus-infected airway epithelial cells. J Virol 81, 1401–1411.[CrossRef]
    [Google Scholar]
  20. Lund, J., Sato, A., Akira, S., Medzhitov, R. & Iwasaki, A. ( 2003; ). Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med 198, 513–520.[CrossRef]
    [Google Scholar]
  21. Malathi, K., Dong, B., Gale, M., Jr & Silverman, R. H. ( 2007; ). Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 448, 816–819.[CrossRef]
    [Google Scholar]
  22. Malmgaard, L. ( 2004; ). Induction and regulation of IFNs during viral infections. J Interferon Cytokine Res 24, 439–454.[CrossRef]
    [Google Scholar]
  23. Malmgaard, L., Melchjorsen, J., Bowie, A. G., Mogensen, S. C. & Paludan, S. R. ( 2004; ). Viral activation of macrophages through TLR-dependent and -independent pathways. J Immunol 173, 6890–6898.[CrossRef]
    [Google Scholar]
  24. Melchjorsen, J., Jensen, S. B., Malmgaard, L., Rasmussen, S. B., Weber, F., Bowie, A. G., Matikainen, S. & Paludan, S. R. ( 2005; ). Activation of innate defense against a paramyxovirus is mediated by RIG-I and TLR7 and TLR8 in a cell-type-specific manner. J Virol 79, 12944–12951.[CrossRef]
    [Google Scholar]
  25. Mogensen, T. H. & Paludan, S. R. ( 2005; ). Reading the viral signature by Toll-like receptors and other pattern recognition receptors. J Mol Med 83, 180–192.[CrossRef]
    [Google Scholar]
  26. Pichlmair, A., Schulz, O., Tan, C. P., Naslund, T. I., Liljestrom, 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]
  27. Rasmussen, S. B., Sorensen, L. N., Malmgaard, L., Ank, N., Baines, J. D., Chen, Z. J. & Paludan, S. R. ( 2007; ). Type I IFN production during HSV infection is controlled by cell-type specific viral recognition by TLR9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems. J Virol 81, 13315–13324.[CrossRef]
    [Google Scholar]
  28. Takahasi, K., Yoneyama, M., Nishihori, T., Hirai, R., Kumeta, H., Narita, R., Gale, M., Jr, Inagaki, F. & Fujita, T. ( 2008; ). Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol Cell 29, 428–440.[CrossRef]
    [Google Scholar]
  29. Weber, F., Wagner, V., Rasmussen, S. B., Hartmann, R. & Paludan, S. R. ( 2006; ). Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J Virol 80, 5059–5064.[CrossRef]
    [Google Scholar]
  30. Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S. & Fujita, T. ( 2004; ). The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5, 730–737.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.005389-0
Loading
/content/journal/jgv/10.1099/vir.0.005389-0
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