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Volume 30, Number 11—November 2024
Research

Antiviral Susceptibility of Swine-Origin Influenza A Viruses Isolated from Humans, United States

Rongyuan Gao1, Philippe Noriel Q. Pascua1, Anton Chesnokov, Ha T. Nguyen, Timothy M. Uyeki, Vasiliy P. Mishin, Natosha Zanders, Dan Cui, Yunho Jang, Joyce Jones, Juan De La Cruz, Han Di, Charles Todd Davis, and Larisa V. GubarevaComments to Author 
Author affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Main Article

Figure

Susceptibility of variant viruses to NA inhibitors based on subtype and NA lineage in study of antiviral susceptibility of swine-origin influenza A viruses isolated from humans, United States. A) Susceptibility of A(H1N1)v (n = 15), A(H1N2)v (n = 14), and A(H3N2)v (n = 21) viruses to NA inhibitors determined in a fluorescence-based assay (29). The IC50s of viruses lacking known or suspected molecular markers that reduce inhibition by NA inhibitors were used to calculate the subtype-specific median IC50s (baseline susceptibility). B, C) Effect of NA lineage on inhibition by NA inhibitors. IC50s obtained in NA inhibition assay were grouped according to their respective NA lineage: N1-classical (n = 7, closed diamond), N1-pdm09 (n = 8, open diamond), N2-1998 (n = 12, closed square), or N2-2002 (n = 23, open square). Horizontal bars and numbers indicate median IC50s. IC50, 50% inhibitory concentration; Lan, laninamivir; NA, neuraminidase; Ose, oseltamivir; Per, peramivir; Zan, zanamivir.

Figure. Susceptibility of variant viruses to NA inhibitors based on subtype and NA lineage in study of antiviral susceptibility of swine-origin influenza A viruses isolated from humans, United States. A) Susceptibility of A(H1N1)v (n = 15), A(H1N2)v (n = 14), and A(H3N2)v (n = 21) viruses to NA inhibitors determined in a fluorescence-based assay (29). The IC50s of viruses lacking known or suspected molecular markers that reduce inhibition by NA inhibitors were used to calculate the subtype-specific median IC50s (baseline susceptibility). B, C) Effect of NA lineage on inhibition by NA inhibitors. IC50s obtained in NA inhibition assay were grouped according to their respective NA lineage: N1-classical (n = 7, closed diamond), N1-pdm09 (n = 8, open diamond), N2-1998 (n = 12, closed square), or N2-2002 (n = 23, open square). Horizontal bars and numbers indicate median IC50s. IC50, 50% inhibitory concentration; Lan, laninamivir; NA, neuraminidase; Ose, oseltamivir; Per, peramivir; Zan, zanamivir.

Main Article

References
  1. Vincent  A, Awada  L, Brown  I, Chen  H, Claes  F, Dauphin  G, et al. Review of influenza A virus in swine worldwide: a call for increased surveillance and research. Zoonoses Public Health. 2014;61:4–17. DOIPubMedGoogle Scholar
  2. Scholtissek  C, Bürger  H, Kistner  O, Shortridge  KF. The nucleoprotein as a possible major factor in determining host specificity of influenza H3N2 viruses. Virology. 1985;147:287–94. DOIPubMedGoogle Scholar
  3. Ito  T, Couceiro  JN, Kelm  S, Baum  LG, Krauss  S, Castrucci  MR, et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol. 1998;72:7367–73. DOIPubMedGoogle Scholar
  4. Zhou  NN, Senne  DA, Landgraf  JS, Swenson  SL, Erickson  G, Rossow  K, et al. Genetic reassortment of avian, swine, and human influenza A viruses in American pigs. J Virol. 1999;73:8851–6. DOIPubMedGoogle Scholar
  5. Olsen  CW. The emergence of novel swine influenza viruses in North America. Virus Res. 2002;85:199–210. DOIPubMedGoogle Scholar
  6. World Health Organization. International health regulations, 2nd edition. Geneva: The Organization; 2005.
  7. Council of State and Territorial Epidemiologists. Council of State and Territorial Epidemiologists Position statement: national reporting for initial detections of novel influenza A viruses [cited 2024 Jun 17]. https://cdn.ymaws.com/www.cste.org/resource/resmgr/PS/07-ID-01.pdf
  8. Shu  B, Garten  R, Emery  S, Balish  A, Cooper  L, Sessions  W, et al. Genetic analysis and antigenic characterization of swine origin influenza viruses isolated from humans in the United States, 1990-2010. Virology. 2012;422:151–60. DOIPubMedGoogle Scholar
  9. Dawood  FS, Jain  S, Finelli  L, Shaw  MW, Lindstrom  S, Garten  RJ, et al.; Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009;360:2605–15. DOIPubMedGoogle Scholar
  10. Garten  RJ, Davis  CT, Russell  CA, Shu  B, Lindstrom  S, Balish  A, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325:197–201. DOIPubMedGoogle Scholar
  11. Anderson  TK, Chang  J, Arendsee  ZW, Venkatesh  D, Souza  CK, Kimble  JB, et al. Swine influenza A viruses and the tangled relationship with humans. Cold Spring Harb Perspect Med. 2021;11:a038737. DOIPubMedGoogle Scholar
  12. Markin  A, Ciacci Zanella  G, Arendsee  ZW, Zhang  J, Krueger  KM, Gauger  PC, et al. Reverse-zoonoses of 2009 H1N1 pandemic influenza A viruses and evolution in United States swine results in viruses with zoonotic potential. PLoS Pathog. 2023;19:e1011476. DOIPubMedGoogle Scholar
  13. World Health Organization. Standardization of terminology for the influenza virus variants infecting humans: update [cited 2024 Jun 17]. https://www.who.int/publications/m/item/standardization-of-terminology-for-the-influenza-virus-variants-infecting-humans-update
  14. Jhung  MA, Epperson  S, Biggerstaff  M, Allen  D, Balish  A, Barnes  N, et al. Outbreak of variant influenza A(H3N2) virus in the United States. Clin Infect Dis. 2013;57:1703–12. DOIPubMedGoogle Scholar
  15. Sleeman  K, Mishin  VP, Guo  Z, Garten  RJ, Balish  A, Fry  AM, et al. Antiviral susceptibility of variant influenza A(H3N2)v viruses isolated in the United States from 2011 to 2013. Antimicrob Agents Chemother. 2014;58:2045–51. DOIPubMedGoogle Scholar
  16. Nelson  MI, Stratton  J, Killian  ML, Janas-Martindale  A, Vincent  AL. Continual reintroduction of human pandemic H1N1 influenza A viruses into swine in the United States, 2009 to 2014. J Virol. 2015;89:6218–26. DOIPubMedGoogle Scholar
  17. Webby  RJ, Swenson  SL, Krauss  SL, Gerrish  PJ, Goyal  SM, Webster  RG. Evolution of swine H3N2 influenza viruses in the United States. J Virol. 2000;74:8243–51. DOIPubMedGoogle Scholar
  18. Rajão  DS, Walia  RR, Campbell  B, Gauger  PC, Janas-Martindale  A, Killian  ML, et al. Reassortment between swine H3N2 and 2009 pandemic H1N1 in the United States resulted in influenza A viruses with diverse genetic constellations with variable virulence in pigs. J Virol. 2017;91:e01763–16. DOIPubMedGoogle Scholar
  19. Sharma  A, Zeller  MA, Li  G, Harmon  KM, Zhang  J, Hoang  H, et al. Detection of live attenuated influenza vaccine virus and evidence of reassortment in the U.S. swine population. J Vet Diagn Invest. 2020;32:301–11. DOIPubMedGoogle Scholar
  20. Centers for Disease Control and Prevention. Novel influenza A virus infections [cited 2024 Apr 24]. https://gis.cdc.gov/grasp/fluview/Novel_Influenza.html
  21. Cox  NJ, Trock  SC, Burke  SA. Pandemic preparedness and the Influenza Risk Assessment Tool (IRAT). Curr Top Microbiol Immunol. 2014;385:119–36. DOIPubMedGoogle Scholar
  22. World Health Organization. Tool for influenza pandemic risk assessment (TIPRA), version 2 release. January 2020 [cited 2024 Jun 17]. https://www.who.int/publications/i/item/tool-for-influenza-pandemic-risk-assessment-(tipra)-2nd-edition
  23. Jones  JC, Yen  HL, Adams  P, Armstrong  K, Govorkova  EA. Influenza antivirals and their role in pandemic preparedness. Antiviral Res. 2023;210:105499. DOIPubMedGoogle Scholar
  24. Hurt  AC. The epidemiology and spread of drug resistant human influenza viruses. Curr Opin Virol. 2014;8:22–9. DOIPubMedGoogle Scholar
  25. Takashita  E, Ejima  M, Itoh  R, Miura  M, Ohnishi  A, Nishimura  H, et al. A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November to December 2013. Euro Surveill. 2014;19:20666. DOIPubMedGoogle Scholar
  26. World Health Organization. Global Influenza Surveillance Network: manual for the laboratory diagnosis and virological surveillance of influenza. Geneva: The Organization; 2011.
  27. Shepard  SS, Meno  S, Bahl  J, Wilson  MM, Barnes  J, Neuhaus  E. Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler. BMC Genomics. 2016;17:708. DOIPubMedGoogle Scholar
  28. Katoh  K, Standley  DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013;30:772–80. DOIPubMedGoogle Scholar
  29. Okomo-Adhiambo  M, Sleeman  K, Ballenger  K, Nguyen  HT, Mishin  VP, Sheu  TG, et al. Neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective. Viruses. 2010;2:2269–89. DOIPubMedGoogle Scholar
  30. Patel  MC, Flanigan  D, Feng  C, Chesnokov  A, Nguyen  HT, Elal  AA, et al. An optimized cell-based assay to assess influenza virus replication by measuring neuraminidase activity and its applications for virological surveillance. Antiviral Res. 2022;208:105457. DOIPubMedGoogle Scholar
  31. World Health Organization. Meetings of the WHO working group on surveillance of influenza antiviral susceptibility – Geneva, November 2011 and June 2012. Wkly Epidemiol Rec. 2012;87:369–74.PubMedGoogle Scholar
  32. World Health Organization. Laboratory methodologies for testing the antiviral susceptibility of influenza viruses: neuraminidase inhibitor (NAI) [cited 2024 Jun 17]. https://www.who.int/teams/global-influenza-programme/laboratory-network/quality-assurance/antiviral-susceptibility-influenza/neuraminidase-inhibitor
  33. World Health Organization. Laboratory methodologies for testing the antiviral susceptibility of influenza viruses: polymerase acidic (PA) inhibitor, baloxavir [cited 2024 Jun 17]. https://www.who.int/teams/global-influenza-programme/laboratory-network/quality-assurance/antiviral-susceptibility-influenza/polymerase-acidic-protein-inhibitor
  34. Boltz  DA, Douangngeun  B, Phommachanh  P, Sinthasak  S, Mondry  R, Obert  C, et al. Emergence of H5N1 avian influenza viruses with reduced sensitivity to neuraminidase inhibitors and novel reassortants in Lao People’s Democratic Republic. J Gen Virol. 2010;91:949–59. DOIPubMedGoogle Scholar
  35. Hurt  AC, Lee  RT, Leang  SK, Cui  L, Deng  YM, Phuah  SP, et al. Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation. Euro Surveill. 2011;16:19884. DOIPubMedGoogle Scholar
  36. Mishin  VP, Patel  MC, Chesnokov  A, De La Cruz  J, Nguyen  HT, Lollis  L, et al. Susceptibility of influenza A, B, C, and D viruses to baloxavir. Emerg Infect Dis. 2019;25:1969–72. DOIPubMedGoogle Scholar
  37. Omoto  S, Speranzini  V, Hashimoto  T, Noshi  T, Yamaguchi  H, Kawai  M, et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci Rep. 2018;8:9633. DOIPubMedGoogle Scholar
  38. Stevaert  A, Dallocchio  R, Dessì  A, Pala  N, Rogolino  D, Sechi  M, et al. Mutational analysis of the binding pockets of the diketo acid inhibitor L-742,001 in the influenza virus PA endonuclease. J Virol. 2013;87:10524–38. DOIPubMedGoogle Scholar
  39. Govorkova  EA, Takashita  E, Daniels  RS, Fujisaki  S, Presser  LD, Patel  MC, et al. Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2018-2020. Antiviral Res. 2022;200:105281. DOIPubMedGoogle Scholar
  40. Gubareva  LV, Mishin  VP, Patel  MC, Chesnokov  A, Nguyen  HT, De La Cruz  J, et al. Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons. Euro Surveill. 2019;24:1800666. DOIPubMedGoogle Scholar
  41. Takashita  E, Daniels  RS, Fujisaki  S, Gregory  V, Gubareva  LV, Huang  W, et al. Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017-2018. Antiviral Res. 2020;175:104718. DOIPubMedGoogle Scholar
  42. Corti  D, Voss  J, Gamblin  SJ, Codoni  G, Macagno  A, Jarrossay  D, et al. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science. 2011;333:850–6. DOIPubMedGoogle Scholar
  43. Dreyfus  C, Laursen  NS, Kwaks  T, Zuijdgeest  D, Khayat  R, Ekiert  DC, et al. Highly conserved protective epitopes on influenza B viruses. Science. 2012;337:1343–8. DOIPubMedGoogle Scholar
  44. Leung  RC, Ip  JD, Chen  LL, Chan  WM, To  KK. Global emergence of neuraminidase inhibitor-resistant influenza A(H1N1)pdm09 viruses with I223V and S247N mutations: implications for antiviral resistance monitoring. Lancet Microbe. 2024;5:627–8. DOIPubMedGoogle Scholar
  45. Patel  M, Nguyen  HT, Pascua  PNQ, Gao  R, Steel  J, Kondor  RJ, et al. Multicountry spread of influenza A(H1N1)pdm09 viruses with reduced inhibition by oseltamivir, May 2023–February 2024. Emerg Infect Dis. 2024;30:1410–5. DOIPubMedGoogle Scholar
  46. Takashita  E, Fujisaki  S, Morita  H, Nagata  S, Miura  H, Matsuura  Y, et al. A community cluster of influenza A(H3N2) virus infection with reduced susceptibility to baloxavir due to a PA E199G substitution in Japan, February to March 2023. Euro Surveill. 2023;28:2300501. DOIPubMedGoogle Scholar
  47. World Health Organization. 2024. Influenza at the human-animal interface summary and risk assessment, 26 February 2024 [cited 2024 Jun 17]. https://www.who.int/publications/m/item/influenza-at-the-human-animal-interface-summary-and-assessment-26--february-2024
  48. Cogdale  J, Kele  B, Myers  R, Harvey  R, Lofts  A, Mikaiel  T, et al.; Influenza A(H1N2)v Incident Management Team. A case of swine influenza A(H1N2)v in England, November 2023. Euro Surveill. 2024;29:2400002. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.

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