1887

Abstract

Interferon regulatory factor 3 (IRF3) is a key transcription factor involved in the induction of interferon (IFN) in response to viral infection. Rotavirus non-structural protein NSP1 binds to and targets IRF3 for proteasome degradation early post-infection. Mutational analysis of cysteine and histidine residues within the conserved N-terminal zinc-binding domain in NSP1 of bovine rotavirus strain B641 abolished IRF3 degradation in transfected cells. Thus, the integrity of the zinc-binding domain in NSP1 is important for degradation of IRF3. In contrast to bovine strain B641, IRF3 was stable in cells infected with porcine rotavirus strain OSU and OSU NSP1 bound only weakly to IRF3. Both B641 NSP1 and OSU NSP1 were stabilized in cells or cell-free extracts in the presence of the proteasome inhibitor MG132 and when the zinc-binding domain was disrupted by site-directed mutagenesis. Data from the B641 analyses that show IRF3 degradation is dependent on the presence of NSP1 and the integrity of the N-terminal zinc-binding domain, coupled with the regulated stability of IRF3 and NSP1 by the proteasome, collectively support the hypothesis that NSP1 is an E3 ubiquitin ligase.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82255-0
2007-02-01
2019-10-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/2/613.html?itemId=/content/journal/jgv/10.1099/vir.0.82255-0&mimeType=html&fmt=ahah

References

  1. Aravind, L., Iyer, L. M. & Koonin, E. V. ( 2003; ). Scores of RINGS but no PHDs in ubiquitin signaling. Cell Cycle 2, 123–126.[CrossRef]
    [Google Scholar]
  2. Au, W. C., Moore, P. A., Lowther, W., Juang, Y. T. & Pitha, P. M. ( 1995; ). Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes. Proc Natl Acad Sci U S A 92, 11657–11661.[CrossRef]
    [Google Scholar]
  3. Barlow, P. N., Luisi, B., Milner, A., Elliott, M. & Everett, R. ( 1994; ). Structure of the C3HC4 domain by 1H-nuclear magnetic resonance spectroscopy. A new structural class of zinc-finger. J Mol Biol 237, 201–211.[CrossRef]
    [Google Scholar]
  4. Barro, M. & Patton, J. T. ( 2005; ). Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3. Proc Natl Acad Sci U S A 102, 4114–4119.[CrossRef]
    [Google Scholar]
  5. Basler, C. F., Mikulasova, A., Martinez-Sobrido, L., Paragas, J., Muhlberger, E., Bray, M., Klenk, H. D., Palese, P. & Garcia-Sastre, A. ( 2003; ). The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol 77, 7945–7956.[CrossRef]
    [Google Scholar]
  6. Brzozka, 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 Virol 79, 7673–7681.[CrossRef]
    [Google Scholar]
  7. Canning, M., Boutell, C., Parkinson, J. & Everett, R. D. ( 2004; ). A RING finger ubiquitin ligase is protected from autocatalyzed ubiquitination and degradation by binding to ubiquitin-specific protease USP7. J Biol Chem 279, 38160–38168.[CrossRef]
    [Google Scholar]
  8. Coscoy, L., Sanchez, D. J. & Ganem, D. ( 2001; ). A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition. J Cell Biol 155, 1265–1273.[CrossRef]
    [Google Scholar]
  9. Daughenbaugh, K. F., Fraser, C. S., Hershey, J. W. & Hardy, M. E. ( 2003; ). The genome-linked protein VPg of the Norwalk virus binds eIF3, suggesting its role in translation initiation complex recruitment. EMBO J 22, 2852–2859.[CrossRef]
    [Google Scholar]
  10. Didcock, L., Young, D. F., Goodbourn, S. & Randall, R. E. ( 1999; ). The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation. J Virol 73, 9928–9933.
    [Google Scholar]
  11. Estes, M. K. ( 2001; ). Rotaviruses and their replication. In Fields Virology, 4th edn, pp. 1747–1785. Edited by D. M. Knipe & P. M. Howley. Philadelphia: Lippincott Williams & Wilkins.
  12. 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 Immunol 4, 491–496.
    [Google Scholar]
  13. Foy, E., Li, K., Wang, C., Sumpter, R., Jr, Ikeda, M., Lemon, S. M. & Gale, M., Jr ( 2003; ). Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 300, 1145–1148.[CrossRef]
    [Google Scholar]
  14. Graff, J. W., Mitzel, D. N., Weisend, C. M., Flenniken, M. L. & Hardy, M. E. ( 2002; ). Interferon regulatory factor 3 is a cellular partner of rotavirus NSP1. J Virol 76, 9545–9550.[CrossRef]
    [Google Scholar]
  15. Hagglund, R. & Roizman, B. ( 2004; ). Role of ICP0 in the strategy of conquest of the host cell by herpes simplex virus 1. J Virol 78, 2169–2178.[CrossRef]
    [Google Scholar]
  16. Hiscott, J., Grandvaux, N., Sharma, S., Tenoever, B. R., Servant, M. J. & Lin, R. ( 2003; ). Convergence of the NF-kappaB and interferon signaling pathways in the regulation of antiviral defense and apoptosis. Ann N Y Acad Sci 1010, 237–248.[CrossRef]
    [Google Scholar]
  17. Horvath, C. M. ( 2004; ). Weapons of STAT destruction. Interferon evasion by paramyxovirus V protein. Eur J Biochem 271, 4621–4628.[CrossRef]
    [Google Scholar]
  18. Jackson, P. K., Eldridge, A. G., Freed, E., Furstenthal, L., Hsu, J. Y., Kaiser, B. K. & Reimann, J. D. ( 2000; ). The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends Cell Biol 10, 429–439.[CrossRef]
    [Google Scholar]
  19. Jennings, S., Martinez-Sobrido, L., Garcia-Sastre, A., Weber, F. & Kochs, G. ( 2005; ). Thogoto virus ML protein suppresses IRF3 function. Virology 331, 63–72.[CrossRef]
    [Google Scholar]
  20. Joazeiro, C. A. & Weissman, A. M. ( 2000; ). RING finger proteins: mediators of ubiquitin ligase activity. Cell 102, 549–552.[CrossRef]
    [Google Scholar]
  21. Juang, Y. T., Lowther, W., Kellum, M., Au, W. C., Lin, R., Hiscott, J. & Pitha, P. M. ( 1998; ). Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc Natl Acad Sci U S A 95, 9837–9842.[CrossRef]
    [Google Scholar]
  22. Mitchell, D. B. & Both, G. W. ( 1990; ). Conservation of a potential metal binding motif despite extensive sequence diversity in the rotavirus nonstructural protein NS53. Virology 174, 618–621.[CrossRef]
    [Google Scholar]
  23. Nishio, M., Garcin, D., Simonet, V. & Kolakofsky, D. ( 2002; ). The carboxyl segment of the mumps virus V protein associates with Stat proteins in vitro via a tryptophan-rich motif. Virology 300, 92–99.[CrossRef]
    [Google Scholar]
  24. Parashar, U. D., Gibson, C. J., Bresse, J. S. & Glass, R. I. ( 2006; ). Rotavirus and severe childhood diarrhea. Emerg Infect Dis 12, 304–306.[CrossRef]
    [Google Scholar]
  25. Parisien, J. P., Lau, J. F., Rodriguez, J. J., Sullivan, B. M., Moscona, A., Parks, G. D., Lamb, R. A. & Horvath, C. M. ( 2001; ). The V protein of human parainfluenza virus 2 antagonizes type I interferon responses by destabilizing signal transducer and activator of transcription 2. Virology 283, 230–239.[CrossRef]
    [Google Scholar]
  26. Patton, J. T., Taraporewala, Z., Chen, D., Chizhikov, V., Jones, M., Elhelu, A., Collins, M., Kearney, K., Wagner, M. & other authors ( 2001; ). Effect of intragenic rearrangement and changes in the 3′ consensus sequence on NSP1 expression and rotavirus replication. J Virol 75, 2076–2086.[CrossRef]
    [Google Scholar]
  27. Pereira, H. G., Azeredo, R. S., Fialho, A. M. & Vidal, M. N. P. ( 1984; ). Genomic heterogeneity of simian rotavirus SA11. J Gen Virol 65, 815–818.[CrossRef]
    [Google Scholar]
  28. Pickart, C. M. ( 2001; ). Mechanisms underlying ubiquitination. Annu Rev Biochem 70, 503–533.[CrossRef]
    [Google Scholar]
  29. Pina-Vazquez, C., De Nova-Ocampo, M., Guzman-Leon, S. & Padilla-Noriega, L. ( 2007; ). Post-translational regulation of rotavirus protein NSP1 expression in mammalian cells. Arch Virol (in press). doi:10.1007/s00705-006-0850-8
    [Google Scholar]
  30. Pulendran, B. & Ahmed, R. ( 2006; ). Translating innate immunity into immunological memory: implications for vaccine development. Cell 124, 849–863.[CrossRef]
    [Google Scholar]
  31. Talon, J., Horvath, C. M., Polley, R., Basler, C. F., Muster, T., Palese, P. & Garcia-Sastre, A. ( 2000; ). Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J Virol 74, 7989–7996.[CrossRef]
    [Google Scholar]
  32. Taniguchi, K., Kojima, K. & Urasawa, S. ( 1996; ). Nondefective rotavirus mutants with an NSP1 gene which has a deletion of 500 nucleotides, including a cysteine-rich zinc finger motif-encoding region (nucleotides 156 to 248), or which has a nonsense codon at nucleotides 153–155. J Virol 70, 4125–4130.
    [Google Scholar]
  33. Theil, K. W., Bohl, E. H. & Agnes, A. G. ( 1977; ). Cell culture propagation of porcine rotavirus (reovirus-like agent). Am J Vet Res 38, 1765–1768.
    [Google Scholar]
  34. Wathelet, M. G., Lin, C. H., Parekh, B. S., Ronco, L. V., Howley, P. M. & Maniatis, T. ( 1998; ). Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell 1, 507–518.[CrossRef]
    [Google Scholar]
  35. Woode, G. N., Kelso, N. E., Simpson, T. F., Gaul, S. K., Evans, L. E. & Babiuk, L. ( 1983; ). Antigenic relationships among some bovine rotaviruses: serum neutralization and cross-protection in gnotobiotic calves. J Clin Microbiol 18, 358–364.
    [Google Scholar]
  36. Yang, Y., Fang, S., Jensen, J. P., Weissman, A. M. & Ashwell, J. D. ( 2000; ). Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 288, 874–877.[CrossRef]
    [Google Scholar]
  37. Yu, Y., Wang, S. E. & Hayward, G. S. ( 2005; ). The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity 22, 59–70.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82255-0
Loading
/content/journal/jgv/10.1099/vir.0.82255-0
Loading

Data & Media loading...

Supplements

vol. , part 2, pp. 613–620

Primers used in plasmid construction and site-directed mutagenesis [ PDF] (65 KB)



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