1887

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Volume 99, Issue 4

Role of p53/NF-κB functional balance in respiratory syncytial virus-induced inflammation response Free

Abstract

The interplay between respiratory syncytial virus (RSV) and the p53 pathway has only been reported in a limited number of studies, yet the underlying abrogation mechanisms of p53 activity during the time course of infection, possibly involving viral proteins, remained unclear. Here, we demonstrate that RSV infection impairs global p53 transcriptional activity, notably via its proteasome-dependent degradation at late stages of infection. We also demonstrate that NS1 and NS2 contribute to the abrogation of p53 activity, and used different experimental strategies (e.g. siRNA, small molecules) to underline the antiviral contribution of p53 in the context of RSV infection. Notably, our study highlights a strong RSV-induced disequilibrium of the p53/NF-κB functional balance, which appears to contribute to the up-regulation of the expression of several proinflammatory cytokines and chemokines.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): inflammation and immune response , NF-kB , p53 , RSV and virus/host interactions
© 2018 The Authors
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2018-04-01
2024-04-20
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References

  1. Blount RE, Morris JA, Savage RE. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med 1956; 92:544–549[PubMed] [Crossref]
     [Google Scholar]
  2. Chanock R, Roizman B, Myers R. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. Am J Hyg 1957; 66:281–290[PubMed]
     [Google Scholar]
  3. Deantonio R, Yarzabal JP, Cruz JP, Schmidt JE, Kleijnen J. Epidemiology of community-acquired pneumonia and implications for vaccination of children living in developing and newly industrialized countries: a systematic literature review. Hum Vaccin Immunother 2016; 12:2422–2440 [View Article][PubMed]
     [Google Scholar]
  4. Stein RT, Bont LJ, Zar H, Polack FP, Park C et al. Respiratory syncytial virus hospitalization and mortality: systematic review and meta-analysis. Pediatr Pulmonol 2017; 52:556–569 [View Article][PubMed]
     [Google Scholar]
  5. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005; 352:1749–1759 [View Article][PubMed]
     [Google Scholar]
  6. Pilie P, Werbel WA, Riddell J, Shu X, Schaubel D et al. Adult patients with respiratory syncytial virus infection: impact of solid organ and hematopoietic stem cell transplantation on outcomes. Transpl Infect Dis 2015; 17:551–557 [View Article][PubMed]
     [Google Scholar]
  7. Pérez-Yarza EG, Moreno A, Lázaro P, Mejías A, Ramilo O. The association between respiratory syncytial virus infection and the development of childhood asthma: a systematic review of the literature. Pediatr Infect Dis J 2007; 26:733–739 [View Article][PubMed]
     [Google Scholar]
  8. Zwaans WA, Mallia P, van Winden ME, Rohde GG. The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease—a systematic review. J Clin Virol 2014; 61:181–188 [View Article][PubMed]
     [Google Scholar]
  9. Somayaji R, Goss CH, Khan U, Neradilek M, Neuzil KM et al. Cystic fibrosis pulmonary exacerbations attributable to respiratory syncytial virus and influenza: a population-based study. Clin Infect Dis 2017; 64:1760–1767 [View Article][PubMed]
     [Google Scholar]
  10. Griffiths C, Drews SJ, Marchant DJ. Respiratory syncytial virus: infection, detection, and new options for prevention and treatment. Clin Microbiol Rev 2017; 30:277–319 [View Article][PubMed]
     [Google Scholar]
  11. Mazur NI, Martinón-Torres F, Baraldi E, Fauroux B, Greenough A et al. Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics. Lancet Respir Med 2015; 3:888–900 [View Article][PubMed]
     [Google Scholar]
  12. Durbin JE, Johnson TR, Durbin RK, Mertz SE, Morotti RA et al. The role of IFN in respiratory syncytial virus pathogenesis. J Immunol 2002; 168:2944–2952 [View Article][PubMed]
     [Google Scholar]
  13. Ramaswamy M, Shi L, Monick MM, Hunninghake GW, Look DC. Specific inhibition of type I interferon signal transduction by respiratory syncytial virus. Am J Respir Cell Mol Biol 2004; 30:893–900 [View Article][PubMed]
     [Google Scholar]
  14. Tripp RA, Oshansky C, Alvarez R. Cytokines and respiratory syncytial virus infection. Proc Am Thorac Soc 2005; 2:147–149 [View Article][PubMed]
     [Google Scholar]
  15. Moore EC, Barber J, Tripp RA. Respiratory syncytial virus (RSV) attachment and nonstructural proteins modify the type I interferon response associated with suppressor of cytokine signaling (SOCS) proteins and IFN-stimulated gene-15 (ISG15). Virol J 2008; 5:116 [View Article][PubMed]
     [Google Scholar]
  16. Spann KM, Tran KC, Chi B, Rabin RL, Collins PL. Suppression of the induction of alpha, beta, and lambda interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages [corrected]. J Virol 2004; 78:4363–4369 [View Article][PubMed]
     [Google Scholar]
  17. Spann KM, Tran KC, Collins PL. Effects of nonstructural proteins NS1 and NS2 of human respiratory syncytial virus on interferon regulatory factor 3, NF-κB, and proinflammatory cytokines. J Virol 2005; 79:5353–5362 [View Article][PubMed]
     [Google Scholar]
  18. Ling Z, Tran KC, Teng MN. Human respiratory syncytial virus nonstructural protein NS2 antagonizes the activation of beta interferon transcription by interacting with RIG-I. J Virol 2009; 83:3734–3742 [View Article][PubMed]
     [Google Scholar]
  19. Lo MS, Brazas RM, Holtzman MJ. Respiratory syncytial virus nonstructural proteins NS1 and NS2 mediate inhibition of Stat2 expression and alpha/beta interferon responsiveness. J Virol 2005; 79:9315–9319 [View Article][PubMed]
     [Google Scholar]
  20. Ramaswamy M, Shi L, Varga SM, Barik S, Behlke MA et al. Respiratory syncytial virus nonstructural protein 2 specifically inhibits type I interferon signal transduction. Virology 2006; 344:328–339 [View Article][PubMed]
     [Google Scholar]
  21. Swedan S, Musiyenko A, Barik S. Respiratory syncytial virus nonstructural proteins decrease levels of multiple members of the cellular interferon pathways. J Virol 2009; 83:9682–9693 [View Article][PubMed]
     [Google Scholar]
  22. Elliott J, Lynch OT, Suessmuth Y, Qian P, Boyd CR et al. Respiratory syncytial virus NS1 protein degrades STAT2 by using the Elongin-Cullin E3 ligase. J Virol 2007; 81:3428–3436 [View Article][PubMed]
     [Google Scholar]
  23. Hastie ML, Headlam MJ, Patel NB, Bukreyev AA, Buchholz UJ et al. The human respiratory syncytial virus nonstructural protein 1 regulates type I and type II interferon pathways. Mol Cell Proteomics 2012; 11:108–127 [View Article][PubMed]
     [Google Scholar]
  24. Li Q, Verma IM. NF-κB regulation in the immune system. Nat Rev Immunol 2002; 2:725–734 [View Article][PubMed]
     [Google Scholar]
  25. Fiedler MA, Wernke-Dollries K, Stark JM. Inhibition of viral replication reverses respiratory syncytial virus-induced NF-κB activation and interleukin-8 gene expression in A549 cells. J Virol 1996; 70:9079–9082[PubMed]
     [Google Scholar]
  26. Thomas KW, Monick MM, Staber JM, Yarovinsky T, Carter AB et al. Respiratory syncytial virus inhibits apoptosis and induces NF-κB activity through a phosphatidylinositol 3-kinase-dependent pathway. J Biol Chem 2002; 277:492–501 [View Article][PubMed]
     [Google Scholar]
  27. Tian B, Zhang Y, Luxon BA, Garofalo RP, Casola A et al. Identification of NF-κB-dependent gene networks in respiratory syncytial virus-infected cells. J Virol 2002; 76:6800–6814 [View Article][PubMed]
     [Google Scholar]
  28. Choudhary S, Boldogh S, Garofalo R, Jamaluddin M, Brasier AR. Respiratory syncytial virus influences NF-κB-dependent gene expression through a novel pathway involving MAP3K14/NIK expression and nuclear complex formation with NF-κB2. J Virol 2005; 79:8948–8959 [View Article][PubMed]
     [Google Scholar]
  29. Liu P, Li K, Garofalo RP, Brasier AR. Respiratory syncytial virus induces RelA release from cytoplasmic 100-kDa NF-κB2 complexes via a novel retinoic acid-inducible Gene-I·NF-κB-inducing kinase signaling pathway. J Biol Chem 2008; 283:23169–23178 [View Article][PubMed]
     [Google Scholar]
  30. Yoboua F, Martel A, Duval A, Mukawera E, Grandvaux N. Respiratory syncytial virus-mediated NF-κB p65 phosphorylation at serine 536 is dependent on RIG-I, TRAF6, and IKK beta. J Virol 2010; 84:7267–7277 [View Article][PubMed]
     [Google Scholar]
  31. Thornburg NJ, Hayward SL, Crowe JE. Respiratory syncytial virus regulates human microRNAs by using mechanisms involving beta interferon and NF-κB. MBio 2012; 3:e00220-12 [View Article][PubMed]
     [Google Scholar]
  32. Bitko V, Shulyayeva O, Mazumder B, Musiyenko A, Ramaswamy M et al. Nonstructural proteins of respiratory syncytial virus suppress premature apoptosis by an NF-κB-dependent, interferon-independent mechanism and facilitate virus growth. J Virol 2007; 81:1786–1795 [View Article][PubMed]
     [Google Scholar]
  33. Muñoz-Fontela C, Mandinova A, Aaronson SA, Lee SW. Emerging roles of p53 and other tumour-suppressor genes in immune regulation. Nat Rev Immunol 2016; 16:741–750 [View Article][PubMed]
     [Google Scholar]
  34. Groskreutz DJ, Monick MM, Yarovinsky TO, Powers LS, Quelle DE et al. Respiratory syncytial virus decreases p53 protein to prolong survival of airway epithelial cells. J Immunol 2007; 179:2741–2747 [View Article][PubMed]
     [Google Scholar]
  35. Eckardt-Michel J, Lorek M, Baxmann D, Grunwald T, Keil GM et al. The fusion protein of respiratory syncytial virus triggers p53-dependent apoptosis. J Virol 2008; 82:3236–3249 [View Article][PubMed]
     [Google Scholar]
  36. Bian T, Gibbs JD, Örvell C, Imani F. Respiratory syncytial virus matrix protein induces lung epithelial cell cycle arrest through a p53 dependent pathway. PLoS One 2012; 7:e38052 [View Article][PubMed]
     [Google Scholar]
  37. Terrier O, Diederichs A, Dubois J, Cartet G, Lina B et al. Influenza NS1 interacts with p53 and alters its binding to p53-responsive genes, in a promoter-dependent manner. FEBS Lett 2013; 587:2965–2971 [View Article][PubMed]
     [Google Scholar]
  38. Lay MK, Bueno SM, Gálvez N, Riedel CA, Kalergis AM. New insights on the viral and host factors contributing to the airway pathogenesis caused by the respiratory syncytial virus. Crit Rev Microbiol 2016; 42:800–812 [View Article][PubMed]
     [Google Scholar]
  39. Bakre A, Wu W, Hiscox J, Spann K, Teng MN et al. Respiratory syncytial virus (RSV) non-structural protein-1 modifies miR-24 expression via TGF-beta. J Gen Virol
     [Google Scholar]
  40. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303:844–848 [View Article][PubMed]
     [Google Scholar]
  41. Ak P, P LAJ. 53 and NF-κB: different strategies for responding to stress lead to a functional antagonism. FASEB J Off Publ Fed Am Soc Exp Biol 2010; 24:3643–3652
     [Google Scholar]
  42. Lane D, Levine A. p53 Research: the past thirty years and the next thirty years. Cold Spring Harb Perspect Biol 2010; 2:a000893 [View Article][PubMed]
     [Google Scholar]
  43. Lane DP. Cancer. p53, guardian of the genome. Nature 1992; 358:15–16 [View Article][PubMed]
     [Google Scholar]
  44. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997; 88:323–331 [View Article][PubMed]
     [Google Scholar]
  45. Sato Y, Tsurumi T. Genome guardian p53 and viral infections. Rev Med Virol 2013; 23:213–220 [View Article][PubMed]
     [Google Scholar]
  46. Lazo PA, Santos CR. Interference with p53 functions in human viral infections, a target for novel antiviral strategies?. Rev Med Virol 2011; 21:285–300 [View Article][PubMed]
     [Google Scholar]
  47. Terrier O, Josset L, Textoris J, Marcel V, Cartet G et al. Cellular transcriptional profiling in human lung epithelial cells infected by different subtypes of influenza A viruses reveals an overall down-regulation of the host p53 pathway. Virol J 2011; 8:285 [View Article][PubMed]
     [Google Scholar]
  48. Terrier O, Marcel V, Cartet G, Lane DP, Lina B et al. Influenza A viruses control expression of proviral human p53 isoforms p53β and Delta133p53α. J Virol 2012; 86:8452–8460 [View Article][PubMed]
     [Google Scholar]
  49. Zhu Z, Yang Y, Wei J, Shao D, Shi Z et al. Type I interferon-mediated immune response against influenza A virus is attenuated in the absence of p53. Biochem Biophys Res Commun 2014; 454:189–195 [View Article][PubMed]
     [Google Scholar]
  50. Yan W, Wei J, Deng X, Shi Z, Zhu Z et al. Transcriptional analysis of immune-related gene expression in p53-deficient mice with increased susceptibility to influenza A virus infection. BMC Med Genomics 2015; 8:52 [View Article][PubMed]
     [Google Scholar]
  51. Nailwal H, Sharma S, Mayank AK, Lal SK. The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via attenuation of host ubiquitin ligase RNF43. Cell Death Dis 2015; 6:e1768 [View Article][PubMed]
     [Google Scholar]
  52. Pollock N, Taylor G, Jobe F, Guzman E. Modulation of the transcription factor NF-κB in antigen-presenting cells by bovine respiratory syncytial virus small hydrophobic protein. J Gen Virol 2017; 98:1587–1599 [View Article][PubMed]
     [Google Scholar]
  53. Olivera A, Moore TW, Hu F, Brown AP, Sun A et al. Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties. Int Immunopharmacol 2012; 12:368–377 [View Article][PubMed]
     [Google Scholar]
  54. Glatthaar-Saalmüller B, Mair KH, Saalmüller A. Antiviral activity of aspirin against RNA viruses of the respiratory tract-an in vitro study. Influenza Other Respir Viruses 2017; 11:85–92 [View Article][PubMed]
     [Google Scholar]
  55. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75:817–825 [View Article][PubMed]
     [Google Scholar]
  56. Hoffmann J, Machado D, Terrier O, Pouzol S, Messaoudi M et al. Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study. Sci Rep 2016; 6:38532 [View Article][PubMed]
     [Google Scholar]
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Role of p53/NF-κB functional balance in respiratory syncytial virus-induced inflammation response
J. Gen. Virol. 99, 489 (2018); https://doi.org/10.1099/jgv.0.001040
/content/journal/jgv/10.1099/jgv.0.001040
/content/journal/jgv/10.1099/jgv.0.001040
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