1887

Abstract

Previous work has documented that the V protein of simian virus 5 (SV5) targets STAT1 for proteasome-mediated degradation, whilst the V protein of human parainfluenza virus type 2 (hPIV2) targets STAT2. Here, it was shown that the processes of ubiquitination and degradation could be reconstructed by using programmed rabbit reticulocyte lysates. Using this system, the addition of bacterially expressed and purified SV5 V protein to programmed lysates was demonstrated to result in the polyubiquitination and degradation of -translated STAT1, but only if human STAT2 was also present. Surprisingly, in the same assay, purified hPIV2 V protein induced the polyubiquitination of both STAT1 and STAT2. In the light of these results, the specificity of degradation of STAT1 and STAT2 by SV5 and hPIV2 in tissue-culture cells was re-examined. As previously reported, STAT1 could not be detected in human cells that expressed SV5 V protein constitutively, whilst STAT2 could not be detected in human cells that expressed hPIV2 V protein, although the levels of STAT1 may also have been reduced in some human cells infected with hPIV2. In contrast, STAT1 could not be detected, whereas STAT2 remained present, in a variety of animal cells, including canine (MDCK) cells, that expressed the V protein of either SV5 or hPIV2. Thus, the V protein of SV5 appears to be highly specific for STAT1 degradation, but the V protein of hPIV2 is more promiscuous.

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2005-01-01
2019-11-14
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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. Chatziandreou, N., Young, D., Andrejeva, J., Goodbourn, S. & Randall, R. E. ( 2002; ). Differences in interferon sensitivity and biological properties of two related isolates of simian virus 5: a model for virus persistence. Virology 293, 234–242.[CrossRef]
    [Google Scholar]
  4. Chen, X., Zhang, Y., Douglas, L. & Zhou, P. ( 2001; ). UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. J Biol Chem 276, 48175–48182.
    [Google Scholar]
  5. Didcock, L., Young, D. F., Goodbourn, S. & Randall, R. E. ( 1999a; ). Sendai virus and simian virus 5 block activation of interferon-responsive genes: importance for virus pathogenesis. J Virol 73, 3125–3133.
    [Google Scholar]
  6. Didcock, L., Young, D. F., Goodbourn, S. & Randall, R. E. ( 1999b; ). The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation. J Virol 73, 9928–9933.
    [Google Scholar]
  7. Garcia-Sastre, A. ( 2004; ). Identification and characterization of viral antagonists of type I interferon in negative-strand RNA viruses. Curr Top Microbiol Immunol 283, 249–280.
    [Google Scholar]
  8. Glickman, M. H. & Ciechanover, A. ( 2002; ). The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82, 373–428.
    [Google Scholar]
  9. 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]
  10. 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-β induction and interferon signaling. Virology 303, 15–32.[CrossRef]
    [Google Scholar]
  11. Horvath, C. M. ( 2004; ). Silencing STATs: lessons from paramyxovirus interferon evasion. Cytokine Growth Factor Rev 15, 117–127.[CrossRef]
    [Google Scholar]
  12. Jackson, P. K., Eldridge, A. G., Freed, E., Furstenthal, L., Hsu, J. Y., Kaiser, B. K. & Reimann, J. D. R. ( 2000; ). The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends Cell Biol 10, 429–439.[CrossRef]
    [Google Scholar]
  13. King, P. & Goodbourn, S. ( 1998; ). STAT1 is inactivated by a caspase. J Biol Chem 273, 8699–8704.[CrossRef]
    [Google Scholar]
  14. Lamb, R. A. & Kolakofsky, D. ( 2001; ). Paramyxoviridae: the viruses and their replication. In Fields Virology, 4th edn, pp. 1305–1340. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Williams & Wilkins.
  15. Leupin, O., Bontron, S. & Strubin, M. ( 2003; ). Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities. J Virol 77, 6274–6283.[CrossRef]
    [Google Scholar]
  16. 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]
  17. 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. Curr Top Microbiol Immunol 283, 197–248.
    [Google Scholar]
  18. Nishio, M., Tsurudome, M., Ito, M., Kawano, M., Komada, H. & Ito, Y. ( 2001; ). High resistance of human parainfluenza type 2 virus protein-expressing cells to the antiviral and anti-cell proliferative activities of alpha/beta interferons: cysteine-rich V-specific domain is required for high resistance to the interferons. J Virol 75, 9165–9176.[CrossRef]
    [Google Scholar]
  19. 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]
  20. 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]
  21. 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]
  22. Pintard, L., Willems, A. & Peter, M. ( 2004; ). Cullin-based ubiquitin ligases: Cul3–BTB complexes join the family. EMBO J 23, 1681–1687.[CrossRef]
    [Google Scholar]
  23. Randall, R. E. & Young, D. F. ( 1991; ). Solid matrix—antibody-antigen complexes induce antigen-specific CD8+ cells that clear a persistent paramyxovirus infection. J Virol 65, 719–726.
    [Google Scholar]
  24. Shiyanov, P., Nag, A. & Raychaudhuri, P. ( 1999; ). Cullin 4A associates with the UV-damaged DNA-binding protein DDB. J Biol Chem 274, 35309–35312.[CrossRef]
    [Google Scholar]
  25. 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]
  26. 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]
  27. Weissman, A. M. ( 2001; ). Themes and variations on ubiquitylation. Nat Rev Mol Cell Biol 2, 169–178.[CrossRef]
    [Google Scholar]
  28. Wertz, I. E., O'Rourke, K. M., Zhang, Z., Dornan, D., Arnott, D., Deshaies, R. J. & Dixit, V. M. ( 2004; ). Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science 303, 1371–1374.[CrossRef]
    [Google Scholar]
  29. Yokosawa, N., Yokota, S., Kubota, T. & Fujii, N. ( 2002; ). C-terminal region of STAT-1α is not necessary for its ubiquitination and degradation caused by mumps virus V protein. J Virol 76, 12683–12690.[CrossRef]
    [Google Scholar]
  30. 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]
  31. 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]
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