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Abstract

Influenza A viruses of the H2N2 subtype sparked a pandemic in 1957 and circulated in humans until 1968. Because A/H2N2 viruses still circulate in wild birds worldwide and human population immunity is low, the transmissibility of six avian A/H2N2 viruses was investigated in the ferret model. None of the avian A/H2N2 viruses was transmitted between ferrets, suggesting that their pandemic risk may be low. The transmissibility, receptor binding preference and haemagglutinin (HA) stability of human A/H2N2 viruses were also investigated. Human A/H2N2 viruses from 1957 and 1958 bound to human-type α2,6-linked sialic acid receptors, but the 1958 virus had a more stable HA, indicating adaptation to replication and spread in the new host. This increased stability was caused by a previously unknown stability substitution G205S in the 1958 H2N2 HA, which became fixed in A/H2N2 viruses after 1958. Although individual substitutions were identified that affected the HA receptor binding and stability properties, they were not found to have a substantial effect on transmissibility of A/H2N2 viruses via the air in the ferret model. Our data demonstrate that A/H2N2 viruses continued to adapt during the first year of pandemic circulation in humans, similar to what was previously shown for the A/H1N1pdm09 virus.

Funding
This study was supported by the:
  • European Research Council (Award 802780)
    • Principle Award Recipient: RobertP de Vries
  • Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Award HHSN272201400008C)
    • Principle Award Recipient: RonAM Fouchier
  • ZonMw (Award 91715372)
    • Principle Award Recipient: SanderHerfst
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/content/journal/jgv/10.1099/jgv.0.001881
2023-08-31
2024-04-28
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References

  1. Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis 2006; 12:9–14 [View Article] [PubMed]
    [Google Scholar]
  2. Blumenfeld HL, Kilbourne ED, Louria DB, Rogers DE. Studies on influenza in the pandemic of 1957-1958. I. An epidemiologic, clinical and serologic investigation of an intrahospital epidemic, with a note on vaccination efficacy. J Clin Invest 1959; 38:199–212 [View Article] [PubMed]
    [Google Scholar]
  3. Choppin B, Ax D, Tamm I. Studies of two kinds of virus particles which comprise influenza A2 virus strains. II. Reactivity with virus inhibitors in normal sera. J Exp Med 1960; 112:921–944 [View Article] [PubMed]
    [Google Scholar]
  4. Lindstrom SE, Cox NJ, Klimov A. Genetic analysis of human H2N2 and early H3N2 influenza viruses, 1957-1972: evidence for genetic divergence and multiple reassortment events. Virology 2004; 328:101–119 [View Article] [PubMed]
    [Google Scholar]
  5. Schäfer JR, Kawaoka Y, Bean WJ, Süss J, Senne D et al. Origin of the pandemic 1957 H2 influenza a virus and the persistence of its possible progenitors in the avian reservoir. Virology 1993; 194:781–788 [View Article] [PubMed]
    [Google Scholar]
  6. Scholtissek C, Rohde W, Von Hoyningen V, Rott R. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 1978; 87:13–20 [View Article] [PubMed]
    [Google Scholar]
  7. Babu TM, Perera R, Wu JT, Fitzgerald T, Nolan C et al. Population serologic immunity to human and avian H2N2 viruses in the United States and Hong Kong for pandemic risk assessment. J Infect Dis 2018; 218:1054–1060 [View Article] [PubMed]
    [Google Scholar]
  8. Ma W, Vincent AL, Gramer MR, Brockwell CB, Lager KM et al. Identification of H2N3 influenza a viruses from swine in the United States. Proc Natl Acad Sci 2007; 104:20949–20954 [View Article] [PubMed]
    [Google Scholar]
  9. Liu J-H, Okazaki K, Bai G-R, Shi W-M, Mweene A et al. Interregional transmission of the internal protein genes of H2 influenza virus in migratory ducks from North America to Eurasia. Virus Genes 2004; 29:81–86 [View Article] [PubMed]
    [Google Scholar]
  10. Gulyaeva M, Sharshov K, Suzuki M, Sobolev I, Sakoda Y et al. Genetic characterization of an H2N2 influenza virus isolated from a muskrat in Western Siberia. J Vet Med Sci 2017; 79:1461–1465 [View Article] [PubMed]
    [Google Scholar]
  11. Ottis K, Sidoli L, Bachmann PA, Webster RG, Kaplan MM. Human influenza a viruses in pigs: isolation of a H3N2 strain antigenically related to A/England/42/72 and evidence for continuous circulation of human viruses in the pig population. Arch Virol 1982; 73:103–108 [View Article] [PubMed]
    [Google Scholar]
  12. Makarova NV, Kaverin NV, Krauss S, Senne D, Webster RG. Transmission of Eurasian avian H2 influenza virus to shorebirds in North America. J Gen Virol 1999; 80:3167–3171 [View Article] [PubMed]
    [Google Scholar]
  13. Munster VJ, Baas C, Lexmond P, Waldenström J, Wallensten A et al. Spatial, temporal, and species variation in prevalence of influenza a viruses in wild migratory birds. PLoS Pathog 2007; 3:e61 [View Article] [PubMed]
    [Google Scholar]
  14. Webby RJ, Webster RG. Are we ready for pandemic influenza?. Science 2003; 302:1519–1522 [View Article] [PubMed]
    [Google Scholar]
  15. Connor RJ, Kawaoka Y, Webster RG, Paulson JC. Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 1994; 205:17–23 [View Article] [PubMed]
    [Google Scholar]
  16. Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A et al. Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol 2000; 74:8502–8512 [View Article] [PubMed]
    [Google Scholar]
  17. Pappas C, Viswanathan K, Chandrasekaran A, Raman R, Katz JM et al. Receptor specificity and transmission of H2N2 subtype viruses isolated from the pandemic of 1957. PLoS One 2010; 5:e11158 [View Article] [PubMed]
    [Google Scholar]
  18. Ito T, Suzuki Y, Takada A, Kawamoto A, Otsuki K et al. Differences in sialic acid-galactose linkages in the chicken egg amnion and allantois influence human influenza virus receptor specificity and variant selection. J Virol 1997; 71:3357–3362 [View Article] [PubMed]
    [Google Scholar]
  19. Gambaryan AS, Tuzikov AB, Piskarev VE, Yamnikova SS, Lvov DK et al. Specification of receptor-binding phenotypes of influenza virus isolates from different hosts using synthetic sialylglycopolymers: non-egg-adapted human H1 and H3 influenza A and influenza B viruses share A common high binding affinity for 6’-sialyl(N-acetyllactosamine). Virology 1997; 232:345–350 [View Article] [PubMed]
    [Google Scholar]
  20. Herfst S, Schrauwen EJA, Linster M, Chutinimitkul S, de Wit E et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 2012; 336:1534–1541 [View Article] [PubMed]
    [Google Scholar]
  21. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 2012; 486:420–428 [View Article] [PubMed]
    [Google Scholar]
  22. Russier M, Yang G, Rehg JE, Wong S-S, Mostafa HH et al. Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein. Proc Natl Acad Sci 2016; 113:1636–1641 [View Article] [PubMed]
    [Google Scholar]
  23. de Wit E, Spronken MIJ, Bestebroer TM, Rimmelzwaan GF, Osterhaus A et al. Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments. Virus Res 2004; 103:155–161 [View Article] [PubMed]
    [Google Scholar]
  24. Kuiken T, Fouchier RAM, Schutten M, Rimmelzwaan GF, van Amerongen G et al. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet 2003; 362:263–270 [View Article] [PubMed]
    [Google Scholar]
  25. de Graaf M, Herfst S, Schrauwen EJA, van den Hoogen BG, Osterhaus A et al. An improved plaque reduction virus neutralization assay for human metapneumovirus. J Virol Methods 2007; 143:169–174 [View Article] [PubMed]
    [Google Scholar]
  26. Asadi S, Gaaloul Ben Hnia N, Barre RS, Wexler AS, Ristenpart WD et al. Influenza A virus is transmissible via aerosolized fomites. Nat Commun 2020; 11:4062 [View Article] [PubMed]
    [Google Scholar]
  27. Kärber G. Beitrag zur kollektiven behandlung pharmakologischer reihenversuche. Archiv f experiment Pathol u Pharmakol 1931; 162:480–483 [View Article]
    [Google Scholar]
  28. Spearman C. The method of “Right and Wrong Cases” (Constant Stimuli) without Gauss’s formula. Br J Psychol 1908; 2:227–242 [View Article]
    [Google Scholar]
  29. Broszeit F, Tzarum N, Zhu X, Nemanichvili N, Eggink D et al. N-Glycolylneuraminic acid as a receptor for influenza A viruses. Cell Rep 2019; 27:3284–3294 [View Article] [PubMed]
    [Google Scholar]
  30. Broszeit F, van Beek RJ, Unione L, Bestebroer TM, Chapla D et al. Glycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses. bioRxiv 2020 [View Article]
    [Google Scholar]
  31. Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 2000; 69:531–569 [View Article] [PubMed]
    [Google Scholar]
  32. Linster M, van Boheemen S, de Graaf M, Schrauwen EJA, Lexmond P et al. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell 2014; 157:329–339 [View Article] [PubMed]
    [Google Scholar]
  33. Carr CM, Chaudhry C, Kim PS. Influenza hemagglutinin is spring-loaded by a metastable native conformation. Proc Natl Acad Sci U S A 1997; 94:14306–14313 [View Article] [PubMed]
    [Google Scholar]
  34. Jones JC, Baranovich T, Marathe BM, Danner AF, Seiler JP et al. Risk assessment of H2N2 influenza viruses from the avian reservoir. J Virol 2014; 88:1175–1188 [View Article] [PubMed]
    [Google Scholar]
  35. Pappas C, Yang H, Carney PJ, Pearce MB, Katz JM et al. Assessment of transmission, pathogenesis and adaptation of H2 subtype influenza viruses in ferrets. Virology 2015; 477:61–71 [View Article] [PubMed]
    [Google Scholar]
  36. Russell CJ. Hemagglutinin stability and its impact on influenza A virus infectivity, pathogenicity, and transmissibility in avians, mice, swine, seals, ferrets, and humans. Viruses 2021; 13:746 [View Article] [PubMed]
    [Google Scholar]
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