1887

Abstract

(MPRV) is a paramyxovirus that was originally isolated from bats, but its host range remains unknown. It was classified as a member of the genus on the basis of structural and genetic features. Like other rubulaviruses it encodes a V protein (MPRV/V) that functions as an interferon (IFN) antagonist. Here we show that MPRV/V differs from the IFN antagonists of other rubulaviruses in that it does not induce the proteasomal degradation of STAT proteins, key factors in the IFN signalling cascade. Rather, MPRV/V prevents the nuclear translocation of STATs in response to IFN stimulation and inhibits the formation of the transcription factor complex ISGF3. We also show that MPRV/V blocks IFN signalling in cells from diverse mammalian species and discuss the IFN response as a barrier to cross-species infections.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82579-0
2007-03-01
2024-10-03
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/3/956.html?itemId=/content/journal/jgv/10.1099/vir.0.82579-0&mimeType=html&fmt=ahah

References

  1. Andrejeva J., Poole E., Young D. F., Goodbourn S., Randall R. E. 2002a; The p127 subunit (DDB1) of the UV-DNA damage repair binding protein is essential for the targeted degradation of STAT1 by the V protein of the paramyxovirus simian virus 5. J Virol 76:11379–11386 [CrossRef]
    [Google Scholar]
  2. Andrejeva J., Young D. F., Goodbourn S., Randall R. E. 2002b; Degradation of STAT1 and STAT2 by the V proteins of simian virus 5 and human parainfluenza virus type 2, respectively: consequences for virus replication in the presence of alpha/beta and gamma interferons. J Virol 76:2159–2167 [CrossRef]
    [Google Scholar]
  3. Andrejeva J., Childs K. S., Young D. F., Carlos T. S., Stock N., Goodbourn S., Randall R. E. 2004; The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN- β promoter. Proc Natl Acad Sci U S A 101:17264–17269 [CrossRef]
    [Google Scholar]
  4. Bossert B., Conzelmann K. K. 2002; Respiratory syncytial virus (RSV) nonstructural (NS) proteins as host range determinants: a chimeric bovine RSV with NS genes from human RSV is attenuated in interferon-competent bovine cells. J Virol 76:4287–4293 [CrossRef]
    [Google Scholar]
  5. Braunstein J., Brutsaert S., Olson R., Schindler C. 2003; STATs dimerize in the absence of phosphorylation. J Biol Chem 278:34133–34140 [CrossRef]
    [Google Scholar]
  6. Chatziandreou N., Stock N., Young D., Andrejeva J., Hagmaier K., McGeoch D. J., Randall R. E. 2004; Relationships and host range of human, canine, simian and porcine isolates of simian virus 5 (parainfluenza virus 5. J Gen Virol 85:3007–3016 [CrossRef]
    [Google Scholar]
  7. Childs K., Stock N., Ross C., Andrejeva J., Hilton L., Skinner M., Randall R., Goodbourn S. 2006; mda-5, but not RIG-I, is a common target for paramyxovirus V proteins. Virology. (in press). doi: 10.1016/j.virol.2006.09.023
  8. Choppin P. W. 1964; Multiplication of a myxovirus (Sv5) with minimal cytopathic effects and without interference. Virology 23:224–233 [CrossRef]
    [Google Scholar]
  9. Conzelmann K. K. 2005; Transcriptional activation of alpha/beta interferon genes: interference by nonsegmented negative-strand RNA viruses. J Virol 79:5241–5248 [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. Fagerlund R., Melen K., Kinnunen L., Julkunen I. 2002; Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5. J Biol Chem 277:30072–30078 [CrossRef]
    [Google Scholar]
  12. Garcia-Sastre A. 2004; Identification and characterisation of viral antagonists of type 1 interferon in negative-strand RNA viruses. In Biology of Negative Strand RNA Viruses pp  249–280 Edited by Kawaoka Y. Berlin/Heidelberg/New York: Springer-Verlag;
    [Google Scholar]
  13. Goodbourn S., Didcock L., Randall R. E. 2000; Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J Gen Virol 81:2341–2364
    [Google Scholar]
  14. Hagmaier K., Stock S., Goodbourn S., Wang L.-F., Randall R. E. 2006; A single amino acid substitution in the V protein of Nipah virus alters its ability to block interferon signalling in cells from different species. J Gen Virol 87:3649–3653 [CrossRef]
    [Google Scholar]
  15. Haller O., Kochs G., Weber F. 2006; The interferon response circuit: induction and suppression by pathogenic viruses. Virology 344:119–130 [CrossRef]
    [Google Scholar]
  16. He B., Paterson R. G., Stock N., Durbin J. E., Durbin R. K., Goodbourn S., Randall R. E., Lamb R. A. 2002; Recovery of paramyxovirus simian virus 5 with a V protein lacking the conserved cysteine-rich domain: the multifunctional V protein blocks both interferon-beta induction and interferon signaling. Virology 303:15–32 [CrossRef]
    [Google Scholar]
  17. Henderson G. W., Laird C., Dermott E., Rima B. K. 1995; Characterization of Mapuera virus: structure, proteins and nucleotide sequence of the gene encoding the nucleocapsid protein. J Gen Virol 76:2509–2518 [CrossRef]
    [Google Scholar]
  18. Horvath C. M. 2004; Silencing STATs: lessons from paramyxovirus interferon evasion. Cytokine Growth Factor Rev 15:117–127 [CrossRef]
    [Google Scholar]
  19. 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]
  20. King P., Goodbourn S. 1994; The beta-interferon promoter responds to priming through multiple independent regulatory elements. J Biol Chem 269:30609–30615
    [Google Scholar]
  21. King P., Goodbourn S. 1998; STAT1 is inactivated by a caspase. J Biol Chem 273:8699–8704 [CrossRef]
    [Google Scholar]
  22. Kubota T., Yokosawa N., Yokota S., Fujii N., Tashiro M., Kato A. 2005; Mumps virus V protein antagonizes interferon without the complete degradation of STAT1. J Virol 79:4451–4459 [CrossRef]
    [Google Scholar]
  23. Li T., Chen X., Garbutt K. C., Zhou P., Zheng N. 2006; Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell 124:105–117 [CrossRef]
    [Google Scholar]
  24. Lin G. Y., Paterson R. G., Richardson C. D., Lamb R. A. 1998; The V protein of the paramyxovirus SV5 interacts with damage-specific DNA binding protein. Virology 249:189–200 [CrossRef]
    [Google Scholar]
  25. Liston P., Briedis D. J. 1994; Measles virus V protein binds zinc. Virology 198:399–404 [CrossRef]
    [Google Scholar]
  26. Masson N., Ellis M., Goodbourn S., Lee K. A. 1992; Cyclic AMP response element-binding protein and the catalytic subunit of protein kinase A are present in F9 embryonal carcinoma cells but are unable to activate the somatostatin promoter. Mol Cell Biol 12:1096–1106
    [Google Scholar]
  27. Nagai Y., Kato A. 2004; Accessory genes of the Paramyxoviridae, a large family of nonsegmented negative-strand RNA viruses, as a focus of active investigation by reverse genetics. In Biology of Negative Strand RNA Viruses pp  197–248 Edited by Kawaoka Y. Berlin/Heidelberg/New York: Springer-Verlag;
    [Google Scholar]
  28. Nishio M., Tsurudome M., Ito M., Ito Y. 2005; Human parainfluenza virus type 4 is incapable of evading the interferon-induced antiviral effect. J Virol 79:14756–14768 [CrossRef]
    [Google Scholar]
  29. Ohno S., Ono N., Takeda M., Takeuchi K., Yanagi Y. 2004; Dissection of measles virus V protein in relation to its ability to block alpha/beta interferon signal transduction. J Gen Virol 85:2991–2999 [CrossRef]
    [Google Scholar]
  30. Palosaari H., Parisien J. P., Rodriguez J. J., Ulane C. M., Horvath C. M. 2003; STAT protein interference and suppression of cytokine signal transduction by measles virus V protein. J Virol 77:7635–7644 [CrossRef]
    [Google Scholar]
  31. 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]
  32. Parisien J. P., Lau J. F., Horvath C. M. 2002a; STAT2 acts as a host range determinant for species-specific paramyxovirus interferon antagonism and simian virus 5 replication. J Virol 76:6435–6441 [CrossRef]
    [Google Scholar]
  33. Parisien J. P., Lau J. F., Rodriguez J. J., Ulane C. M., Horvath C. M. 2002b; Selective STAT protein degradation induced by paramyxoviruses requires both STAT1 and STAT2 but is independent of alpha/beta interferon signal transduction. J Virol 76:4190–4198 [CrossRef]
    [Google Scholar]
  34. Park M. S., Shaw M. L., Munoz-Jordan J., Cros J. F., Nakaya T., Bouvier N., Palese P., Garcia-Sastre A., Basler C. F. 2003; Newcastle disease virus (NDV)-based assay demonstrates interferon-antagonist activity for the NDV V protein and the Nipah virus V, W, and C proteins. J Virol 77:1501–1511 [CrossRef]
    [Google Scholar]
  35. Paterson R. G., Leser G. P., Shaughnessy M. A., Lamb R. A. 1995; The paramyxovirus SV5 V protein binds two atoms of zinc and is a structural component of virions. Virology 208:121–131 [CrossRef]
    [Google Scholar]
  36. Poole E., He B., Lamb R. A., Randall R. E., Goodbourn S. 2002; The V proteins of simian virus 5 and other paramyxoviruses inhibit induction of interferon-beta. Virology 303:33–46 [CrossRef]
    [Google Scholar]
  37. Precious B., Childs K., Fitzpatrick-Swallow V., Goodbourn S., Randall R. E. 2005a; Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1. J Virol 79:13434–13441 [CrossRef]
    [Google Scholar]
  38. Precious B., Young D. F., Andrejeva L., Goodbourn S., Randall R. E. 2005b; In vitro and in vivo specificity of ubiquitination and degradation of STAT1 and STAT2 by the V proteins of the paramyxoviruses simian virus 5 and human parainfluenza virus type 2. J Gen Virol 86:151–158 [CrossRef]
    [Google Scholar]
  39. Randall R. E., Dinwoodie N. 1986; Intranuclear localization of herpes simplex virus immediate-early and delayed-early proteins: evidence that ICP 4 is associated with progeny virus DNA. J Gen Virol 67:2163–2177 [CrossRef]
    [Google Scholar]
  40. Rehberg E., Kelder B., Hoal E. G., Pestka S. 1982; Specific molecular activities of recombinant and hybrid leukocyte interferons. J Biol Chem 257:11497–11502
    [Google Scholar]
  41. Rodriguez J. J., Parisien J. P., Horvath C. M. 2002; Nipah virus V protein evades alpha and gamma interferons by preventing STAT1 and STAT2 activation and nuclear accumulation. J Virol 76:11476–11483 [CrossRef]
    [Google Scholar]
  42. Rodriguez J. J., Wang L. F., Horvath C. M. 2003; Hendra virus V protein inhibits interferon signaling by preventing STAT1 and STAT2 nuclear accumulation. J Virol 77:11842–11845 [CrossRef]
    [Google Scholar]
  43. Rodriguez J. J., Cruz C. D., Horvath C. M. 2004; Identification of the nuclear export signal and STAT-binding domains of the Nipah virus V protein reveals mechanisms underlying interferon evasion. J Virol 78:5358–5367 [CrossRef]
    [Google Scholar]
  44. Sen G. C. 2001; Viruses and interferons. Annu Rev Microbiol 55:255–281 [CrossRef]
    [Google Scholar]
  45. Sen G. C., Sarkar S. N. 2005; Hitching RIG to action. Nat Immunol 6:1074–1076 [CrossRef]
    [Google Scholar]
  46. Shaffer J. A., Bellini W. J., Rota P. A. 2003; The C protein of measles virus inhibits the type I interferon response. Virology 315:389–397 [CrossRef]
    [Google Scholar]
  47. Shaw M. L., Garcia-Sastre A., Palese P., Basler C. F. 2004; Nipah virus V and W proteins have a common STAT1-binding domain yet inhibit STAT1 activation from the cytoplasmic and nuclear compartments, respectively. J Virol 78:5633–5641 [CrossRef]
    [Google Scholar]
  48. Shuai K., Ziemiecki A., Wilks A. F., Harpur A. G., Sadowski H. B., Gilman M. Z., Darnell J. E. 1993; Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Nature 366:580–583 [CrossRef]
    [Google Scholar]
  49. Stock N., Goodbourn S., Randall R. E. 2005; The anti-interferon mechanisms of paramyxoviruses. In Modulation of Host Gene Expression and Innate Immunity in Viruses pp  115–140 Edited by Palese P., Changeux J.-P. Dordrecht: Springer;
    [Google Scholar]
  50. Takeuchi K., Kadota S. I., Takeda M., Miyajima N., Nagata K. 2003; Measles virus V protein blocks interferon (IFN)-alpha/beta but not IFN-gamma signaling by inhibiting STAT1 and STAT2 phosphorylation. FEBS Lett 545:177–182 [CrossRef]
    [Google Scholar]
  51. Thomas S. M., Lamb R. A., Paterson R. G. 1988; Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5. Cell 54:891–902 [CrossRef]
    [Google Scholar]
  52. Ulane C. M., Horvath C. M. 2002; Paramyxoviruses SV5 and HPIV2 assemble STAT protein ubiquitin ligase complexes from cellular components. Virology 304:160–166 [CrossRef]
    [Google Scholar]
  53. Ulane C. M., Rodriguez J. J., Parisien J. P., Horvath C. M. 2003; STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling. J Virol 77:6385–6393 [CrossRef]
    [Google Scholar]
  54. Ulane C. M., Kentsis A., Cruz C. D., Parisien J. P., Schneider K. L., Horvath C. M. 2005; Composition and assembly of STAT-targeting ubiquitin ligase complexes: paramyxovirus V protein carboxyl terminus is an oligomerization domain. J Virol 79:10180–10189 [CrossRef]
    [Google Scholar]
  55. Wansley E. K., Parks G. D. 2002; Naturally occurring substitutions in the P/V gene convert the noncytopathic paramyxovirus simian virus 5 into a virus that induces alpha/beta interferon synthesis and cell death. J Virol 76:10109–10121 [CrossRef]
    [Google Scholar]
  56. Yokosawa N., Yokota S., Kubota T., Fujii N. 2002; C-terminal region of STAT-1alpha is not necessary for its ubiquitination and degradation caused by mumps virus V protein. J Virol 76:12683–12690 [CrossRef]
    [Google Scholar]
  57. Yokota S., Saito H., Kubota T., Yokosawa N., Amano K., Fujii N. 2003; Measles virus suppresses interferon-alpha signaling pathway: suppression of Jak1 phosphorylation and association of viral accessory proteins, C and V, with interferon-alpha receptor complex. Virology 306:135–146 [CrossRef]
    [Google Scholar]
  58. 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]
  59. Young D. F., Didcock L., Goodbourn S., Randall R. E. 2000; Paramyxoviridae use distinct virus-specific mechanisms to circumvent the interferon response. Virology 269:383–390 [CrossRef]
    [Google Scholar]
  60. Young D. F., Chatziandreou N., He B., Goodbourn S., Lamb R. A., Randall R. E. 2001; Single amino acid substitution in the V protein of simian virus 5 differentiates its ability to block interferon signaling in human and murine cells. J Virol 75:3363–3370 [CrossRef]
    [Google Scholar]
  61. Young D. F., Andrejeva L., Livingstone A., Goodbourn S., Lamb R. A., Collins P. L., Elliott R. M., Randall R. E. 2003; Virus replication in engineered human cells that do not respond to interferons. J Virol 77:2174–2181 [CrossRef]
    [Google Scholar]
  62. Zeller H. G., Karabatsos N., Calisher C. H., Digoutte J. P., Murphy F. A., Shope R. E. 1989; Electron microscopy and antigenic studies of uncharacterized viruses. I. Evidence suggesting the placement of viruses in families Arenaviridae, Paramyxoviridae, or Poxviridae. Arch Virol 108:191–209 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.82579-0
Loading
/content/journal/jgv/10.1099/vir.0.82579-0
Loading

Data & Media loading...

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