1887

Abstract

Human parainfluenza virus type 1 (HPIV-1) and Sendai virus (SeV) are highly homologous in structure and sequence, whilst maintaining distinct host ranges. These viruses express accessory proteins from their P/C gene that are known to have activities against innate immunity. The accessory proteins expressed from the P/C gene of these viruses are different. In addition to the nested set of C proteins, SeV expresses V protein from edited P mRNA, which is not expressed by HPIV-1. This study evaluated the host specificity and role of the P/C gene products in anti-interferon (IFN) and anti-apoptosis activity by characterizing a recombinant SeV, rSeVhP, in which the SeV P/C gene was replaced with that of HPIV-1. Unlike SeV, rSeVhP infection strongly activated IFN regulatory transcription factor (IRF)-3 and nuclear factor-B, resulting in an increased level of IFN- induction compared with SeV in murine cells. In contrast, activation of IRF-3 was not observed in rSeVhP-infected human A549 cells. rSeVhPSV, which expressed SeV V protein from an inserted gene in rSeVhP, induced less IFN- than rSeVhP, suggesting that V contributes to the suppression of IFN production in murine cells. Furthermore, rSeVhP induced apoptotic cell death in murine but not in A549 cells. These data indicate the functional difference in P/C gene products from SeV and HPIV-1 in antagonizing IFN induction and apoptosis, which is likely to be one of the major factors for pathogenicity in specific hosts.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.011700-0
2009-08-01
2019-11-22
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/8/1906.html?itemId=/content/journal/jgv/10.1099/vir.0.011700-0&mimeType=html&fmt=ahah

References

  1. Alymova, I. V., Taylor, G., Takimoto, T., Lin, T. H., Chand, P., Babu, Y. S., Li, C., Xiong, X. & Portner, A. ( 2004; ). Efficacy of novel hemagglutinin–neuraminidase inhibitors BCX 2798 and BCX 2855 against human parainfluenza viruses in vitro and in vivo. Antimicrob Agents Chemother 48, 1495–1502.[CrossRef]
    [Google Scholar]
  2. 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]
  3. Bartlett, E. J., Cruz, A. M., Esker, J., Castano, A., Schomacker, H., Surman, S. R., Hennessey, M., Boonyaratanakornkit, J., Pickles, R. J. & other authors ( 2008a; ). Human parainfluenza virus type 1 C proteins are nonessential proteins that inhibit the host interferon and apoptotic responses and are required for efficient replication in nonhuman primates. J Virol 82, 8965–8977.[CrossRef]
    [Google Scholar]
  4. Bartlett, E. J., Hennessey, M., Skiadopoulos, M. H., Schmidt, A. C., Collins, P. L., Murphy, B. R. & Pickles, R. J. ( 2008b; ). Role of interferon in the replication of human parainfluenza virus type 1 wild type and mutant viruses in human ciliated airway epithelium. J Virol 82, 8059–8070.[CrossRef]
    [Google Scholar]
  5. Bousse, T., Matrosovich, T., Portner, A., Kato, A., Nagai, Y. & Takimoto, T. ( 2002; ). The long noncoding region of the human parainfluenza virus type 1 F gene contributes to the read-through transcription at the M-F gene junction. J Virol 76, 8244–8251.[CrossRef]
    [Google Scholar]
  6. Bousse, T., Chambers, R. L., Scroggs, R. A., Portner, A. & Takimoto, T. ( 2006; ). Human parainfluenza virus type 1 but not Sendai virus replicates in human respiratory cells despite IFN treatment. Virus Res 121, 23–32.[CrossRef]
    [Google Scholar]
  7. 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]
  8. Curran, J., Boeck, R. & Kolakofsky, D. ( 1991; ). The Sendai virus P gene expresses both an essential protein and an inhibitor of RNA synthesis by shuffling modules via mRNA editing. EMBO J 10, 3079–3085.
    [Google Scholar]
  9. 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]
  10. Dillon, P. J. & Parks, G. D. ( 2007; ). Role for the phosphoprotein P subunit of the paramyxovirus polymerase in limiting induction of host cell antiviral responses. J Virol 81, 11116–11127.[CrossRef]
    [Google Scholar]
  11. Fuerst, T. R., Niles, E. G., Studier, F. W. & Moss, B. ( 1986; ). Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A 83, 8122–8126.[CrossRef]
    [Google Scholar]
  12. Garcin, D., Marq, J. B., Goodbourn, S. & Kolakofsky, D. ( 2003; ). The amino-terminal extensions of the longer Sendai virus C proteins modulate pY701-Stat1 and bulk Stat1 levels independently of interferon signaling. J Virol 77, 2321–2329.[CrossRef]
    [Google Scholar]
  13. Gotoh, B., Komatsu, T., Takeuchi, K. & Yokoo, J. ( 2001; ). Paramyxovirus accessory proteins as interferon antagonists. Microbiol Immunol 45, 787–800.[CrossRef]
    [Google Scholar]
  14. Haller, O., Kochs, G. & Weber, F. ( 2006; ). The interferon response circuit: induction and suppression by pathogenic viruses. Virology 344, 119–130.[CrossRef]
    [Google Scholar]
  15. 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]
  16. Heylbroeck, C., Balachandran, S., Servant, M. J., DeLuca, C., Barber, G. N., Lin, R. & Hiscott, J. ( 2000; ). The IRF-3 transcription factor mediates Sendai virus-induced apoptosis. J Virol 74, 3781–3792.[CrossRef]
    [Google Scholar]
  17. Iwamura, T., Yoneyama, M., Yamaguchi, K., Suhara, W., Mori, W., Shiota, K., Okabe, Y., Namiki, H. & Fujita, T. ( 2001; ). Induction of IRF-3/-7 kinase and NF-κB in response to double-stranded RNA and virus infection: common and unique pathways. Genes Cells 6, 375–388.[CrossRef]
    [Google Scholar]
  18. Kato, A., Sakai, Y., Shioda, T., Kondo, T., Nakanishi, M. & Nagai, Y. ( 1996; ). Initiation of Sendai virus multiplication from transfected cDNA or RNA with negative or positive sense. Genes Cells 1, 569–579.[CrossRef]
    [Google Scholar]
  19. Kato, A., Kiyotani, K., Sakai, Y., Yoshida, T. & Nagai, Y. ( 1997; ). The paramyxovirus, Sendai virus, V protein encodes a luxury function required for viral pathogenesis. EMBO J 16, 578–587.[CrossRef]
    [Google Scholar]
  20. Kato, A., Cortese-Grogan, C., Moyer, S. A., Sugahara, F., Sakaguchi, T., Kubota, T., Otsuki, N., Kohase, M., Tashiro, M. & Nagai, Y. ( 2004; ). Characterization of the amino acid residues of Sendai virus C protein that are critically involved in its interferon antagonism and RNA synthesis down-regulation. J Virol 78, 7443–7454.[CrossRef]
    [Google Scholar]
  21. 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]
  22. Kato, A., Kiyotani, K., Kubota, T., Yoshida, T., Tashiro, M. & Nagai, Y. ( 2007; ). Importance of the anti-interferon capacity of Sendai virus C protein for pathogenicity in mice. J Virol 81, 3264–3271.[CrossRef]
    [Google Scholar]
  23. Kiyotani, K., Sakaguchi, T., Kato, A., Nagai, Y. & Yoshida, T. ( 2007; ). Paramyxovirus Sendai virus V protein counteracts innate virus clearance through IRF-3 activation, but not via interferon, in mice. Virology 359, 82–91.[CrossRef]
    [Google Scholar]
  24. Komatsu, T., Takeuchi, K., Yokoo, J. & Gotoh, B. ( 2002; ). Sendai virus C protein impairs both phosphorylation and dephosphorylation processes of Stat1. FEBS Lett 511, 139–144.[CrossRef]
    [Google Scholar]
  25. Komatsu, T., Takeuchi, K., Yokoo, J. & Gotoh, B. ( 2004; ). C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-β production. Virology 325, 137–148.[CrossRef]
    [Google Scholar]
  26. Koyama, A. H., Irie, H., Kato, A., Nagai, Y. & Adachi, A. ( 2003; ). Virus multiplication and induction of apoptosis by Sendai virus: role of the C proteins. Microbes Infect 5, 373–378.[CrossRef]
    [Google Scholar]
  27. Matsuoka, Y., Curran, J., Pelet, T., Kolakofsky, D., Ray, R. & Compans, R. W. ( 1991; ). The P gene of human parainfluenza virus type 1 encodes P and C proteins but not a cysteine-rich V protein. J Virol 65, 3406–3410.
    [Google Scholar]
  28. Peters, K., Chattopadhyay, S. & Sen, G. C. ( 2008; ). IRF-3 activation by Sendai virus infection is required for cellular apoptosis and avoidance of persistence. J Virol 82, 3500–3508.[CrossRef]
    [Google Scholar]
  29. Power, U. F., Ryan, K. W. & Portner, A. ( 1992; ). The P genes of human parainfluenza virus type 1 clinical isolates are polycistronic and microheterogeneous. Virology 189, 340–343.[CrossRef]
    [Google Scholar]
  30. Precious, B., Young, D. F., Andrejeva, L., Goodbourn, S. & Randall, R. E. ( 2005; ). 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]
  31. Randall, R. E. & Goodbourn, S. ( 2008; ). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 89, 1–47.[CrossRef]
    [Google Scholar]
  32. Sangster, M., Smith, F. S., Coleclough, C. & Hurwitz, J. L. ( 1995; ). Human parainfluenza virus type 1 immunization of infant mice protects from subsequent Sendai virus infection. Virology 212, 13–19.[CrossRef]
    [Google Scholar]
  33. Strahle, L., Marq, J. B., Brini, A., Hausmann, S., Kolakofsky, D. & Garcin, D. ( 2007; ). Activation of the beta interferon promoter by unnatural Sendai virus infection requires RIG-I and is inhibited by viral C proteins. J Virol 81, 12227–12237.[CrossRef]
    [Google Scholar]
  34. Takimoto, T., Bousse, T. & Portner, A. ( 2000; ). Molecular cloning and expression of human parainfluenza virus type 1 L gene. Virus Res 70, 45–53.[CrossRef]
    [Google Scholar]
  35. Talon, J., Horvath, C. M., Polley, R., Basler, C. F., Muster, T., Palese, P. & García-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]
  36. Van Cleve, W., Amaro-Carambot, E., Surman, S. R., Bekisz, J., Collins, P. L., Zoon, K. C., Murphy, B. R., Skiadopoulos, M. H. & Bartlett, E. J. ( 2006; ). Attenuating mutations in the P/C gene of human parainfluenza virus type 1 (HPIV1) vaccine candidates abrogate the inhibition of both induction and signaling of type I interferon (IFN) by wild-type HPIV1. Virology 352, 61–73.[CrossRef]
    [Google Scholar]
  37. 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]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.011700-0
Loading
/content/journal/jgv/10.1099/vir.0.011700-0
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