1887

Journal of General Virology header logo

Volume 90, Issue 8

Host specificity of the anti-interferon and anti-apoptosis activities of parainfluenza virus P/C gene products Free

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.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.011700-0
2009-08-01
2024-04-19
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- κ B 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
Host specificity of the anti-interferon and anti-apoptosis activities of parainfluenza virus P/C gene products
J. Gen. Virol. 90, 1906 (2009); https://doi.org/10.1099/vir.0.011700-0
/content/journal/jgv/10.1099/vir.0.011700-0
/content/journal/jgv/10.1099/vir.0.011700-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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