Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 28, Number 2—February 2022
Perspective

Viral Interference between Respiratory Viruses

Jocelyne Piret and Guy BoivinComments to Author 
Author affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Québec‒Université Laval, Quebec City, Quebec, Canada

Main Article

Table 1

Evasion mechanisms of human respiratory viruses to type I interferon*

Virus Viral proteins interfering with interferon induction and signaling Reference
Human rhinovirus
IFN induction: VPg interferes with viral RNA recognition by RNA sensors; 2A protease reduces cap-dependent translation of cellular mRNA; 2A and 3C proteases cleave MAVS. IFN signaling: 3C protease inhibits activation of antiviral protein complexes.
(5)
Human metapneumovirus
IFN induction: G interferes with TLR4 signaling; SH inhibits NF-κB signaling; M2.2 protein interferes with MAVS and inhibits IRF7 phosphorylation. IFN signaling: SH prevents STAT1 phosphorylation.
(6)
Respiratory syncytial virus
IFN induction: NS1 inhibits IRF3 phosphorylation, inhibits TRIM25-mediated RIG-I ubiquitination; NS2 binds to RIG-I and reduces IRF3 activation; G reduces IFN-λ production. IFN signaling: NS1 promotes OASL degradation and inhibits IFNAR1 expression; NS1 and NS2 induce STAT2 degradation.
(5)
Influenza virus
IFN induction: NS1 interferes with viral RNA sensing by TLR and RIG-I, binds to viral RNA and reduces RIG-I activation, inhibits TRIM25-mediated RIG-I ubiquitination and prevents the export of cellular mRNA to cytoplasm; PB1-F2 and PB2 interfere with MAVS; PA reduces IRF3 activation; M2 protein interacts with MAVS. IFN signaling: NS1 reduces PKR and OASL activation; HA induces IFNAR1 degradation; SOCS inhibits STAT2; NP and M2 protein interfere with PKR activation.
(7)
Severe acute respiratory syndrome coronavirus IFN induction: NSP14 methylates capped RNA transcripts; NSP15 cleaves 5′-polyuridines from viral RNA; NSP16 and NSP10 methylate viral RNA cap; N protein inhibits TRIM25-mediated RIG-I ubiquitination; NSP3 deubiquitinates cellular substrates (possibly RIG-I) and inhibits IRF3 phosphorylation; ORF9b targets MAVS, TRAF3 and TRAF6 to degradation; M protein impedes TRAF3/TBK1/IKKε complex formation; ORF3b might target MAVS; NSP1 promotes cellular mRNA degradation and prevents host mRNA translation. IFN signaling: ORF3a promotes IFNAR1 degradation; NSP1 decreases STAT1 phosphorylation; ORF6 inhibits nuclear translocation of STAT1. (8)

*G, glycoprotein; HA, hemagglutinin; IFN, interferon; IFNAR1, IFN-α/β receptor 1; IRF, IFN regulatory factor; M, matrix; MAVS, mitochondrial antiviral signaling protein; N, nucleocapsid; NP, nucleocapsid protein; NS, nonstructural; NSP, nonstructural protein, OASL, 2’-5′ oligoadenylate synthetase-ribonuclease L; ORF, open reading frame; PA, polymerase acidic; PB, polymerase basic; PKR, protein kinase receptor; RIG-I, retinoic acid‒inducible gene I; SH, viroporin protein; SOCS, suppressor of cytokine signaling; STAT, signal transducer and activator of transcription; TANK, TRAF family member‒associated NF-κB activator; TBK1, TANK binding kinase 1; TLR, Toll-like receptor; TRAF, tumor necrosis factor receptor‒associated factor; TRIM25, tripartite motif containing 25.

Main Article

References
  1. Zhang  AJ, Lee  AC, Chan  JF, Liu  F, Li  C, Chen  Y, et al. Coinfection by severe acute respiratory syndrome coronavirus 2 and influenza A(H1N1)pdm09 virus enhances the severity of pneumonia in golden Syrian hamsters. Clin Infect Dis. 2021;72:e97892. DOIPubMedGoogle Scholar
  2. Laurie  KL, Horman  W, Carolan  LA, Chan  KF, Layton  D, Bean  A, et al. Evidence for viral interference and cross-reactive protective immunity between influenza B virus lineages. J Infect Dis. 2018;217:54859. DOIPubMedGoogle Scholar
  3. Chan  KF, Carolan  LA, Korenkov  D, Druce  J, McCaw  J, Reading  PC, et al. Investigating viral interference between influenza A virus and human respiratory syncytial virus in a ferret model of infection. J Infect Dis. 2018;218:40617. DOIPubMedGoogle Scholar
  4. Schneider  WM, Chevillotte  MD, Rice  CM. Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol. 2014;32:51345. DOIPubMedGoogle Scholar
  5. Kikkert  M. Innate immune evasion by human respiratory RNA viruses. J Innate Immun. 2020;12:420. DOIPubMedGoogle Scholar
  6. Soto  JA, Gálvez  NMS, Benavente  FM, Pizarro-Ortega  MS, Lay  MK, Riedel  C, et al. Human metapneumovirus: mechanisms and molecular targets used by the virus to avoid the immune system. Front Immunol. 2018;9:2466. DOIPubMedGoogle Scholar
  7. Li  C, Wang  T, Zhang  Y, Wei  F. Evasion mechanisms of the type I interferons responses by influenza A virus. Crit Rev Microbiol. 2020;46:42032. DOIPubMedGoogle Scholar
  8. Sa Ribero  M, Jouvenet  N, Dreux  M, Nisole  S. Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog. 2020;16:e1008737. DOIPubMedGoogle Scholar
  9. Huang  IC, Li  W, Sui  J, Marasco  W, Choe  H, Farzan  M. Influenza A virus neuraminidase limits viral superinfection. J Virol. 2008;82:483443. DOIPubMedGoogle Scholar
  10. Shinjoh  M, Omoe  K, Saito  N, Matsuo  N, Nerome  K. In vitro growth profiles of respiratory syncytial virus in the presence of influenza virus. Acta Virol. 2000;44:917.PubMedGoogle Scholar
  11. Goto  H, Ihira  H, Morishita  K, Tsuchiya  M, Ohta  K, Yumine  N, et al. Enhanced growth of influenza A virus by coinfection with human parainfluenza virus type 2. Med Microbiol Immunol (Berl). 2016;205:20918. DOIPubMedGoogle Scholar
  12. Nickbakhsh  S, Mair  C, Matthews  L, Reeve  R, Johnson  PCD, Thorburn  F, et al. Virus-virus interactions impact the population dynamics of influenza and the common cold. Proc Natl Acad Sci U S A. 2019;116:2714250. DOIPubMedGoogle Scholar
  13. Voroshilova  MK. Potential use of nonpathogenic enteroviruses for control of human disease. In: Melnick JL, editor. Progress in medical virology. Basel: Karger; 1989. p. 191–202.
  14. Chumakov  MP, Voroshilova  MK, Antsupova  AS, Boĭko  VM, Blinova  MI, Priĭmiagi  LS, et al. [Live enteroviral vaccines for the emergency nonspecific prevention of mass respiratory diseases during fall-winter epidemics of influenza and acute respiratory diseases] [in Russian]. Zh Mikrobiol Epidemiol Immunobiol. 1992;11‒12:3740.PubMedGoogle Scholar
  15. Rijsbergen  LC, van Dijk  LLA, Engel  MFM, de Vries  RD, de Swart  RL. In vitro modelling of respiratory virus infections in human airway epithelial cells: a systematic review. Front Immunol. 2021;12:683002. DOIPubMedGoogle Scholar
  16. Shou  S, Liu  M, Yang  Y, Kang  N, Song  Y, Tan  D, et al. Animal models for COVID-19: hamsters, mouse, ferret, mink, tree shrew, and non-human primates. Front Microbiol. 2021;12:626553. DOIPubMedGoogle Scholar
  17. Laurie  KL, Guarnaccia  TA, Carolan  LA, Yan  AW, Aban  M, Petrie  S, et al. Interval between infections and viral hierarchy are determinants of viral interference following influenza virus infection in a ferret model. J Infect Dis. 2015;212:170110. DOIPubMedGoogle Scholar
  18. Greer  RM, McErlean  P, Arden  KE, Faux  CE, Nitsche  A, Lambert  SB, et al. Do rhinoviruses reduce the probability of viral co-detection during acute respiratory tract infections? J Clin Virol. 2009;45:105. DOIPubMedGoogle Scholar
  19. Price  OH, Sullivan  SG, Sutterby  C, Druce  J, Carville  KS. Using routine testing data to understand circulation patterns of influenza A, respiratory syncytial virus and other respiratory viruses in Victoria, Australia. Epidemiol Infect. 2019;147:e221. DOIPubMedGoogle Scholar
  20. Geiser  J, Boivin  G, Huang  S, Constant  S, Kaiser  L, Tapparel  C, et al. RSV and HMPV infections in 3D tissue cultures: mechanisms involved in virus-host and virus-virus interactions. Viruses. 2021;13:139. DOIPubMedGoogle Scholar
  21. Arden  KE, Greer  RM, Wang  CYT, Mackay  IM. Genotypic diversity, circulation patterns and co-detections among rhinoviruses in Queensland, 2001. Access Microbiol. 2019;2:acmi000075.PubMedGoogle Scholar
  22. Mackay  IM, Lambert  SB, Faux  CE, Arden  KE, Nissen  MD, Sloots  TP, et al. Community-wide, contemporaneous circulation of a broad spectrum of human rhinoviruses in healthy Australian preschool-aged children during a 12-month period. J Infect Dis. 2013;207:143341. DOIPubMedGoogle Scholar
  23. Wu  A, Mihaylova  VT, Landry  ML, Foxman  EF. Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study. Lancet Microbe. 2020;1:e25462. DOIPubMedGoogle Scholar
  24. Karppinen  S, Toivonen  L, Schuez-Havupalo  L, Waris  M, Peltola  V. Interference between respiratory syncytial virus and rhinovirus in respiratory tract infections in children. Clin Microbiol Infect. 2016;22:208.e16. DOIPubMedGoogle Scholar
  25. Achten  NB, Wu  P, Bont  L, Blanken  MO, Gebretsadik  T, Chappell  JD, et al. Interference between respiratory syncytial virus and human rhinovirus infection in infancy. J Infect Dis. 2017;215:11026. DOIPubMedGoogle Scholar
  26. Dee  K, Goldfarb  DM, Haney  J, Amat  JA, Herder  V, Stewart  M, et al. Human rhinovirus infection blocks SARS-CoV-2 replication within the respiratory epithelium: implications for COVID-19 epidemiology. J Infect Dis. 2021;224:318. DOIPubMedGoogle Scholar
  27. Cheemarla  NR, Watkins  TA, Mihaylova  VT, Wang  B, Zhao  D, Wang  G, et al. Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics. J Exp Med. 2021;218:e20210583. DOIPubMedGoogle Scholar
  28. Sonoguchi  T, Naito  H, Hara  M, Takeuchi  Y, Fukumi  H. Cross-subtype protection in humans during sequential, overlapping, and/or concurrent epidemics caused by H3N2 and H1N1 influenza viruses. J Infect Dis. 1985;151:818. DOIPubMedGoogle Scholar
  29. Van Kerkhove  MD, Mounts  AW. 2009 versus 2010 comparison of influenza activity in southern hemisphere temperate countries. Influenza Other Respir Viruses. 2011;5:3759. DOIPubMedGoogle Scholar
  30. Yang  Y, Wang  Z, Ren  L, Wang  W, Vernet  G, Paranhos-Baccalà  G, et al. Influenza A/H1N1 2009 pandemic and respiratory virus infections, Beijing, 2009-2010. PLoS One. 2012;7:e45807. DOIPubMedGoogle Scholar
  31. Anestad  G, Vainio  K, Hungnes  O. Interference between outbreaks of epidemic viruses. Scand J Infect Dis. 2007;39:6534. DOIPubMedGoogle Scholar
  32. Nishimura  N, Nishio  H, Lee  MJ, Uemura  K. The clinical features of respiratory syncytial virus: lower respiratory tract infection after upper respiratory tract infection due to influenza virus. Pediatr Int. 2005;47:4126. DOIPubMedGoogle Scholar
  33. van Asten  L, Bijkerk  P, Fanoy  E, van Ginkel  A, Suijkerbuijk  A, van der Hoek  W, et al. Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections. Influenza Other Respir Viruses. 2016;10:1426. DOIPubMedGoogle Scholar
  34. Gröndahl  B, Ankermann  T, von Bismarck  P, Rockahr  S, Kowalzik  F, Gehring  S, et al. The 2009 pandemic influenza A(H1N1) coincides with changes in the epidemiology of other viral pathogens causing acute respiratory tract infections in children. Infection. 2014;42:3038. DOIPubMedGoogle Scholar
  35. Mak  GC, Wong  AH, Ho  WY, Lim  W. The impact of pandemic influenza A (H1N1) 2009 on the circulation of respiratory viruses 2009-2011. Influenza Other Respir Viruses. 2012;6:e610. DOIPubMedGoogle Scholar
  36. Green  HK, Ellis  J, Galiano  M, Watson  JM, Pebody  RG. Critical care surveillance: insights into the impact of the 2010/11 influenza season relative to the 2009/10 pandemic season in England. Euro Surveill. 2013;18:20499. DOIPubMedGoogle Scholar
  37. Casalegno  JS, Ottmann  M, Bouscambert-Duchamp  M, Valette  M, Morfin  F, Lina  B. Impact of the 2009 influenza A(H1N1) pandemic wave on the pattern of hibernal respiratory virus epidemics, France, 2009. Euro Surveill. 2010;15:19485. DOIPubMedGoogle Scholar
  38. Meningher  T, Hindiyeh  M, Regev  L, Sherbany  H, Mendelson  E, Mandelboim  M. Relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses. Influenza Other Respir Viruses. 2014;8:42230. DOIPubMedGoogle Scholar
  39. Ånestad  G, Nordbø  SA. Virus interference. Did rhinoviruses activity hamper the progress of the 2009 influenza A (H1N1) pandemic in Norway? Med Hypotheses. 2011;77:11324. DOIPubMedGoogle Scholar
  40. Linde  A, Rotzén-Ostlund  M, Zweygberg-Wirgart  B, Rubinova  S, Brytting  M. Does viral interference affect spread of influenza? Euro Surveill. 2009;14:19354. DOIPubMedGoogle Scholar
  41. Casalegno  JS, Ottmann  M, Duchamp  MB, Escuret  V, Billaud  G, Frobert  E, et al. Rhinoviruses delayed the circulation of the pandemic influenza A (H1N1) 2009 virus in France. Clin Microbiol Infect. 2010;16:3269. DOIPubMedGoogle Scholar
  42. Zheng  X, Song  Z, Li  Y, Zhang  J, Wang  XL. Possible interference between seasonal epidemics of influenza and other respiratory viruses in Hong Kong, 2014-2017. BMC Infect Dis. 2017;17:772. DOIPubMedGoogle Scholar
  43. Gonzalez  AJ, Ijezie  EC, Balemba  OB, Miura  TA. Attenuation of influenza A virus disease severity by viral coinfection in a mouse model. J Virol. 2018;92:e0088118. DOIPubMedGoogle Scholar
  44. Park  S, Michelow  IC, Choe  YJ. Shifting patterns of respiratory virus activity following social distancing measures for COVID-19 in South Korea. J Infect Dis. 2021;jiab231.
  45. Leung  NHL, Chu  DKW, Shiu  EYC, Chan  KH, McDevitt  JJ, Hau  BJP, et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med. 2020;26:67680. DOIPubMedGoogle Scholar
  46. Alfi  O, Yakirevitch  A, Wald  O, Wandel  O, Izhar  U, Oiknine-Djian  E, et al. Human nasal and lung tissues infected ex vivo with SARS-CoV-2 provide insights into differential tissue-specific and virus-specific innate immune responses in the upper and lower respiratory tract. J Virol. 2021;95:e0013021. DOIPubMedGoogle Scholar
  47. Vignuzzi  M, López  CB. Defective viral genomes are key drivers of the virus-host interaction. Nat Microbiol. 2019;4:107587. DOIPubMedGoogle Scholar
  48. Scott  PD, Meng  B, Marriott  AC, Easton  AJ, Dimmock  NJ. Defective interfering influenza A virus protects in vivo against disease caused by a heterologous influenza B virus. J Gen Virol. 2011;92:212232. DOIPubMedGoogle Scholar
  49. Easton  AJ, Scott  PD, Edworthy  NL, Meng  B, Marriott  AC, Dimmock  NJ. A novel broad-spectrum treatment for respiratory virus infections: influenza-based defective interfering virus provides protection against pneumovirus infection in vivo. Vaccine. 2011;29:277784. DOIPubMedGoogle Scholar
  50. Musuuza  JS, Watson  L, Parmasad  V, Putman-Buehler  N, Christensen  L, Safdar  N. Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and meta-analysis. PLoS One. 2021;16:e0251170. DOIPubMedGoogle Scholar

Main Article

Page created: October 27, 2021
Page updated: January 22, 2022
Page reviewed: January 22, 2022
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external