1887

Journal of General Virology header logo

Volume 98, Issue 6

Loss of Sendai virus C protein leads to accumulation of RIG-I immunostimulatory defective interfering RNA Open Access

Abstract

Retinoic acid inducible gene (RIG-I)-mediated innate immunity plays a pivotal role in defence against virus infections. Previously we have shown that Sendai virus (SeV) defective interfering (DI) RNA functions as an exclusive and potent RIG-I ligand in DI-RNA-rich SeV-Cantell infected cells. To further understand how RIG-I is activated during SeV infection, we used a different interferon (IFN)-inducing SeV strain, recombinant SeVΔC, which, in contrast to SeV-Cantell is believed to stimulate IFN production due to the lack of the SeV IFN antagonist protein C. Surprisingly, we found that in SevΔC-infected cells, DI RNAs also functioned as an exclusive RIG-I ligand. Infections with wild-type SeV failed to generate any RIG-I-associated immunostimulatory RNA and this correlated with the lack of DI genomes in infected cells, as well as with the absence of cellular innate immune responses. Supplementation of the C protein in the context of SeVΔC infection led to a reduction in the number of DI RNAs, further supporting the potential role of the C protein as a negative regulator of DI generation and/or accumulation. Our findings indicate that limiting DI genome production is an important function of viral IFN antagonist proteins.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): C protein , defective interfering RNA , RIG-I and Sendai
© 2017 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000815
2017-06-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/6/1282.html?itemId=/content/journal/jgv/10.1099/jgv.0.000815&mimeType=html&fmt=ahah

References

  1. Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002; 20:197–216 [View Article][PubMed]
     [Google Scholar]
  2. Baum A, García-Sastre A. Induction of type I interferon by RNA viruses: cellular receptors and their substrates. Amino Acids 2010; 38:1283–1299 [View Article][PubMed]
     [Google Scholar]
  3. Hornung V, Ellegast J, Kim S, Brzózka K, Jung A et al. 5′-Triphosphate RNA is the ligand for RIG-I. Science 2006; 314:994–997 [View Article][PubMed]
     [Google Scholar]
  4. Pichlmair A, Schulz O, Tan CP, Näslund TI, Liljeström P et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 2006; 314:997–1001 [View Article][PubMed]
     [Google Scholar]
  5. Schlee M, Roth A, Hornung V, Hagmann CA, Wimmenauer V et al. Recognition of 5′ triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity 2009; 31:25–34 [View Article][PubMed]
     [Google Scholar]
  6. Lu C, Xu H, Ranjith-Kumar CT, Brooks MT, Hou TY et al. The structural basis of 5′ triphosphate double-stranded RNA recognition by RIG-I C-terminal domain. Structure 2010; 18:1032–1043 [View Article][PubMed]
     [Google Scholar]
  7. Jiang F, Ramanathan A, Miller MT, Tang GQ, Gale M et al. Structural basis of RNA recognition and activation by innate immune receptor RIG-I. Nature 2011; 479:423–427 [View Article][PubMed]
     [Google Scholar]
  8. Kowalinski E, Lunardi T, Mccarthy AA, Louber J, Brunel J et al. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA. Cell 2011; 147:423–435 [View Article][PubMed]
     [Google Scholar]
  9. Schmidt A, Schwerd T, Hamm W, Hellmuth JC, Cui S et al. 5′-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I. Proc Natl Acad Sci USA 2009; 106:12067–12072 [View Article][PubMed]
     [Google Scholar]
  10. Goubau D, Schlee M, Deddouche S, Pruijssers AJ, Zillinger T et al. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates. Nature 2014; 514:372–375 [View Article][PubMed]
     [Google Scholar]
  11. Baum A, Sachidanandam R, García-Sastre A. Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing. Proc Natl Acad Sci USA 2010; 107:16303–16308 [View Article][PubMed]
     [Google Scholar]
  12. Lazzarini RA, Keene JD, Schubert M. The origins of defective interfering particles of the negative-strand RNA viruses. Cell 1981; 26:145–154 [View Article][PubMed]
     [Google Scholar]
  13. Marcus PI, Sekellick MJ. Defective interfering particles with covalently linked [±] RNA induce interferon. Nature 1977; 266:815–819 [View Article][PubMed]
     [Google Scholar]
  14. Shingai M, Ebihara T, Begum NA, Kato A, Honma T et al. Differential type I IFN-inducing abilities of wild-type versus vaccine strains of measles virus. J Immunol 2007; 179:6123–6133 [View Article][PubMed]
     [Google Scholar]
  15. Strahle L, Garcin D, Kolakofsky D. Sendai virus defective-interfering genomes and the activation of interferon-beta. Virology 2006; 351:101–111 [View Article][PubMed]
     [Google Scholar]
  16. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006; 441:101–105 [View Article][PubMed]
     [Google Scholar]
  17. Moltedo B, López CB, Pazos M, Becker MI, Hermesh T et al. Cutting edge: stealth influenza virus replication precedes the initiation of adaptive immunity. J Immunol 2009; 183:3569–3573 [View Article][PubMed]
     [Google Scholar]
  18. Tapia K, Kim WK, Sun Y, Mercado-López X, Dunay E et al. Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity. PLoS Pathog 2013; 9:e1003703 [View Article][PubMed]
     [Google Scholar]
  19. Strähle L, Marq JB, Brini A, Hausmann S, Kolakofsky D et al. Activation of the beta interferon promoter by unnatural Sendai virus infection requires RIG-I and is inhibited by viral C proteins. J Virol 2007; 81:12227–12237 [View Article][PubMed]
     [Google Scholar]
  20. Childs K, Stock N, Ross C, Andrejeva J, Hilton L et al. mda-5, but not RIG-I, is a common target for paramyxovirus V proteins. Virology 2007; 359:190–200 [View Article][PubMed]
     [Google Scholar]
  21. Cadd T, Garcin D, Tapparel C, Itoh M, Homma M et al. The Sendai paramyxovirus accessory C proteins inhibit viral genome amplification in a promoter-specific fashion. J Virol 1996; 70:5067–5074[PubMed]
     [Google Scholar]
  22. Curran J, Boeck R, Kolakofsky D. The Sendai virus P gene expresses both an essential protein and an inhibitor of RNA synthesis by shuffling modules via mRNA editing. EMBO J 1991; 10:3079–3085[PubMed]
     [Google Scholar]
  23. Curran J, Marq JB, Kolakofsky D. The Sendai virus nonstructural C proteins specifically inhibit viral mRNA synthesis. Virology 1992; 189:647–656 [View Article][PubMed]
     [Google Scholar]
  24. Tapparel C, Hausmann S, Pelet T, Curran J, Kolakofsky D et al. Inhibition of Sendai virus genome replication due to promoter-increased selectivity: a possible role for the accessory C proteins. J Virol 1997; 71:9588–9599[PubMed]
     [Google Scholar]
  25. Kurotani A, Kiyotani K, Kato A, Shioda T, Sakai Y et al. Sendai virus C proteins are categorically nonessential gene products but silencing their expression severely impairs viral replication and pathogenesis. Genes Cells 1998; 3:111–124 [View Article][PubMed]
     [Google Scholar]
  26. Latorre P, Cadd T, Itoh M, Curran J, Kolakofsky D. The various Sendai virus C proteins are not functionally equivalent and exert both positive and negative effects on viral RNA accumulation during the course of infection. J Virol 1998; 72:5984–5993[PubMed]
     [Google Scholar]
  27. Koyama AH, Irie H, Kato A, Nagai Y, Adachi A. Virus multiplication and induction of apoptosis by Sendai virus: role of the C proteins. Microbes Infect 2003; 5:373–378 [View Article][PubMed]
     [Google Scholar]
  28. Hasan MK, Kato A, Muranaka M, Yamaguchi R, Sakai Y et al. Versatility of the accessory C proteins of Sendai virus: contribution to virus assembly as an additional role. J Virol 2000; 74:5619–5628 [View Article][PubMed]
     [Google Scholar]
  29. Irie T, Nagata N, Yoshida T, Sakaguchi T. Recruitment of Alix/AIP1 to the plasma membrane by Sendai virus C protein facilitates budding of virus-like particles. Virology 2008; 371:108–120 [View Article][PubMed]
     [Google Scholar]
  30. Irie T, Shimazu Y, Yoshida T, Sakaguchi T. The YLDL sequence within Sendai virus M protein is critical for budding of virus-like particles and interacts with Alix/AIP1 independently of C protein. J Virol 2007; 81:2263–2273 [View Article][PubMed]
     [Google Scholar]
  31. Komatsu T, Takeuchi K, Yokoo J, Gotoh B. C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-beta production. Virology 2004; 325:137–148 [View Article][PubMed]
     [Google Scholar]
  32. Garcin D, Marq JB, Strahle L, Le Mercier P, Kolakofsky D. All four Sendai virus C proteins bind Stat1, but only the larger forms also induce its mono-ubiquitination and degradation. Virology 2002; 295:256–265 [View Article][PubMed]
     [Google Scholar]
  33. Strähle L, Garcin D, Le Mercier P, Schlaak JF, Kolakofsky D. Sendai virus targets inflammatory responses, as well as the interferon-induced antiviral state, in a multifaceted manner. J Virol 2003; 77:7903–7913 [View Article][PubMed]
     [Google Scholar]
  34. Huang AS. Defective interfering viruses. Annu Rev Microbiol 1973; 27:101–117 [View Article][PubMed]
     [Google Scholar]
  35. Calain P, Roux L. The rule of six, a basic feature for efficient replication of Sendai virus defective interfering RNA. J Virol 1993; 67:4822–4830[PubMed]
     [Google Scholar]
  36. Mottet-Osman G, Iseni F, Pelet T, Wiznerowicz M, Garcin D et al. Suppression of the Sendai virus M protein through a novel short interfering RNA approach inhibits viral particle production but does not affect viral RNA synthesis. J Virol 2007; 81:2861–2868 [View Article][PubMed]
     [Google Scholar]
  37. Killip MJ, Young DF, Ross CS, Chen S, Goodbourn S et al. Failure to activate the IFN-β promoter by a paramyxovirus lacking an interferon antagonist. Virology 2011; 415:39–46 [View Article][PubMed]
     [Google Scholar]
  38. Chen S, Short JA, Young DF, Killip MJ, Schneider M et al. Heterocellular induction of interferon by negative-sense RNA viruses. Virology 2010; 407:247–255 [View Article][PubMed]
     [Google Scholar]
  39. Senger K, Merika M, Agalioti T, Yie J, Escalante CR et al. Gene repression by coactivator repulsion. Mol Cell 2000; 6:931–937 [View Article][PubMed]
     [Google Scholar]
  40. Zawatzky R, De Maeyer E, de Maeyer-Guignard J. Identification of individual interferon-producing cells by in situ hybridization. Proc Natl Acad Sci USA 1985; 82:1136–1140 [View Article][PubMed]
     [Google Scholar]
  41. Hu J, Sealfon SC, Hayot F, Jayaprakash C, Kumar M et al. Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells. Nucleic Acids Res 2007; 35:5232–5241 [View Article][PubMed]
     [Google Scholar]
  42. Takeuchi K, Komatsu T, Kitagawa Y, Sada K, Gotoh B. Sendai virus C protein plays a role in restricting PKR activation by limiting the generation of intracellular double-stranded RNA. J Virol 2008; 82:10102–10110 [View Article][PubMed]
     [Google Scholar]
  43. Boonyaratanakornkit J, Bartlett E, Schomacker H, Surman S, Akira S et al. The C proteins of human parainfluenza virus type 1 limit double-stranded RNA accumulation that would otherwise trigger activation of MDA5 and protein kinase R. J Virol 2011; 85:1495–1506 [View Article][PubMed]
     [Google Scholar]
  44. Yoshida A, Kawabata R, Honda T, Tomonaga K, Sakaguchi T et al. IFN-β-inducing, unusual viral RNA species produced by paramyxovirus infection accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner. Front Microbiol 2015; 6:804 [View Article][PubMed]
     [Google Scholar]
  45. Pfaller CK, Mastorakos GM, Matchett WE, Ma X, Samuel CE et al. Measles virus defective interfering RNAs are generated frequently and early in the absence of C protein and can be destabilized by adenosine deaminase acting on RNA-1-like hypermutations. J Virol 2015; 89:7735–7747 [View Article][PubMed]
     [Google Scholar]
  46. Pfaller CK, Radeke MJ, Cattaneo R, Samuel CE. Measles virus C protein impairs production of defective copyback double-stranded viral RNA and activation of protein kinase R. J Virol 2014; 88:456–468 [View Article][PubMed]
     [Google Scholar]
  47. Komarova AV, Combredet C, Sismeiro O, Dillies MA, Jagla B et al. Identification of RNA partners of viral proteins in infected cells. RNA Biol 2013; 10:943–956 [View Article][PubMed]
     [Google Scholar]
  48. Li D, Lott WB, Lowry K, Jones A, Thu HM et al. Defective interfering viral particles in acute dengue infections. PLoS One 2011; 6:e19447 [View Article][PubMed]
     [Google Scholar]
  49. Pesko KN, Fitzpatrick KA, Ryan EM, Shi PY, Zhang B et al. Internally deleted WNV genomes isolated from exotic birds in New Mexico: function in cells, mosquitoes, and mice. Virology 2012; 427:10–17 [View Article][PubMed]
     [Google Scholar]
  50. Forrester NL, Guerbois M, Adams AP, Liang X, Weaver SC. Analysis of intrahost variation in venezuelan equine encephalitis virus reveals repeated deletions in the 6-kilodalton protein gene. J Virol 2011; 85:8709–8717 [View Article][PubMed]
     [Google Scholar]
  51. Saira K, Lin X, DePasse JV, Halpin R, Twaddle A et al. Sequence analysis of in vivo defective interfering-like RNA of influenza A H1N1 pandemic virus. J Virol 2013; 87:8064–8074 [View Article][PubMed]
     [Google Scholar]
  52. Petterson E, Stormoen M, Evensen Ø, Mikalsen AB, Haugland Ø. Natural infection of Atlantic salmon (Salmo salar L.) with salmonid alphavirus 3 generates numerous viral deletion mutants. J Gen Virol 2013; 94:1945–1954 [View Article][PubMed]
     [Google Scholar]
  53. Garcin D, Marq JB, Iseni F, Martin S, Kolakofsky D. A short peptide at the amino terminus of the Sendai virus C protein acts as an independent element that induces STAT1 instability. J Virol 2004; 78:8799–8811 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000815
Loading
Loss of Sendai virus C protein leads to accumulation of RIG-I immunostimulatory defective interfering RNA
J. Gen. Virol. 98, 1282 (2017); https://doi.org/10.1099/jgv.0.000815
/content/journal/jgv/10.1099/jgv.0.000815
/content/journal/jgv/10.1099/jgv.0.000815
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