1887

Abstract

Over the last decade, an increasing proportion of circulating human influenza A(H3N2) viruses exhibited haemagglutination activity that was sensitive to neuraminidase inhibitors. This change in haemagglutination as compared to older circulating A(H3N2) viruses prompted an investigation of the underlying molecular basis. Recent human influenza A(H3N2) viruses were found to agglutinate turkey erythrocytes in a manner that could be blocked with either oseltamivir or neuraminidase-specific antisera, indicating that agglutination was driven by neuraminidase, with a low or negligible contribution of haemagglutinin. Using representative virus recombinants it was shown that the haemagglutinin of a recent A(H3N2) virus indeed had decreased activity to agglutinate turkey erythrocytes, while its neuraminidase displayed increased haemagglutinating activity. Viruses with chimeric and mutant neuraminidases were used to identify the amino acid substitution histidine to arginine at position 150 flanking the neuraminidase catalytic site as the determinant of this neuraminidase-mediated haemagglutination. An analysis of publicly available neuraminidase gene sequences showed that viruses with histidine at position 150 were rapidly replaced by viruses with arginine at this position between 2005 and 2008, in agreement with the phenotypic data. As a consequence of neuraminidase-mediated haemagglutination of recent A(H3N2) viruses and poor haemagglutination via haemagglutinin, haemagglutination inhibition assays with A(H3N2) antisera are no longer useful to characterize the antigenic properties of the haemagglutinin of these viruses for vaccine strain selection purposes. Continuous monitoring of the evolution of these viruses and potential consequences for vaccine strain selection remains important.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000809
2017-06-01
2020-01-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/6/1274.html?itemId=/content/journal/jgv/10.1099/jgv.0.000809&mimeType=html&fmt=ahah

References

  1. Nelson MI, Holmes EC. The evolution of epidemic influenza. Nat Rev Genet 2007;8:196–205 [CrossRef][PubMed]
    [Google Scholar]
  2. Monto AS. Influenza: quantifying morbidity and mortality. Am J Med 1987;82:20–25 [CrossRef][PubMed]
    [Google Scholar]
  3. Stöhr K. Influenza—WHO cares. Lancet Infect Dis 2002;2:517 [CrossRef][PubMed]
    [Google Scholar]
  4. Thompson WW, Comanor L, Shay DK. Epidemiology of seasonal influenza: use of surveillance data and statistical models to estimate the burden of disease. J Infect Dis 2006;194:S82–S91 [CrossRef][PubMed]
    [Google Scholar]
  5. WHO 2017; Influenza vaccine viruses and reagents. WHO. www.who.int/influenza/vaccines/virus/en/
  6. Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 2000;69:531–569 [CrossRef][PubMed]
    [Google Scholar]
  7. Wagner R, Matrosovich M, Klenk HD. Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol 2002;12:159–166 [CrossRef][PubMed]
    [Google Scholar]
  8. Liu C, Eichelberger MC, Compans RW, Air GM. Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly, or budding. J Virol 1995;69:1099–1106[PubMed]
    [Google Scholar]
  9. Mitnaul LJ, Matrosovich MN, Castrucci MR, Tuzikov AB, Bovin NV et al. Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus. J Virol 2000;74:6015–6020 [CrossRef][PubMed]
    [Google Scholar]
  10. Richard M, Erny A, Caré B, Traversier A, Barthélémy M et al. Rescue of a H3N2 influenza virus containing a deficient neuraminidase protein by a hemagglutinin with a low receptor-binding affinity. PLoS One 2012;7:e33880 [CrossRef][PubMed]
    [Google Scholar]
  11. Gulati U, Wu W, Gulati S, Kumari K, Waner JL et al. Mismatched hemagglutinin and neuraminidase specificities in recent human H3N2 influenza viruses. Virology 2005;339:12–20 [CrossRef][PubMed]
    [Google Scholar]
  12. Wright P, Neumann G, Kawaoka Y. Orthomyxoviruses. In Howley PM, Knipe DM. (editors) Fields Virology, 1st ed. Wolters Kluwer: Lippincott Williams & Wilkins; 2013; pp.1785–1837
    [Google Scholar]
  13. Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD. Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J Virol 2004;78:12665–12667 [CrossRef][PubMed]
    [Google Scholar]
  14. Morishita T, Kobayashi S, Miyake T, Ishihara Y, Nakajima S et al. Host-specific hemagglutination of influenza A (H1N1) virus. Microbiol Immunol 1993;37:661–665 [CrossRef][PubMed]
    [Google Scholar]
  15. Nobusawa E, Ishihara H, Morishita T, Sato K, Nakajima K. Change in receptor-binding specificity of recent human influenza A viruses (H3N2): a single amino acid change in hemagglutinin altered its recognition of sialyloligosaccharides. Virology 2000;278:587–596 [CrossRef][PubMed]
    [Google Scholar]
  16. Medeiros R, Escriou N, Naffakh N, Manuguerra JC, van der Werf S. Hemagglutinin residues of recent human A(H3N2) influenza viruses that contribute to the inability to agglutinate chicken erythrocytes. Virology 2001;289:74–85 [CrossRef][PubMed]
    [Google Scholar]
  17. Ito T, Suzuki Y, Mitnaul L, Vines A, Kida H et al. Receptor specificity of influenza A viruses correlates with the agglutination of erythrocytes from different animal species. Virology 1997;227:493–499 [CrossRef][PubMed]
    [Google Scholar]
  18. Lin YP, Gregory V, Collins P, Kloess J, Wharton S et al. Neuraminidase receptor binding variants of human influenza A(H3N2) viruses resulting from substitution of aspartic acid 151 in the catalytic site: a role in virus attachment?. J Virol 2010;84:6769–6781 [CrossRef][PubMed]
    [Google Scholar]
  19. Lin YP, Xiong X, Wharton SA, Martin SR, Coombs PJ et al. Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin. Proc Natl Acad Sci USA 2012;109:21474–21479 [CrossRef][PubMed]
    [Google Scholar]
  20. Zhu X, Mcbride R, Nycholat CM, Yu W, Paulson JC et al. Influenza virus neuraminidases with reduced enzymatic activity that avidly bind sialic acid receptors. J Virol 2012;86:13371–13383 [CrossRef][PubMed]
    [Google Scholar]
  21. van Baalen CA, Els C, Sprong L, van Beek R, van der Vries E et al. Detection of nonhemagglutinating influenza A (H3) viruses by enzyme-linked immunosorbent assay in quantitative influenza virus culture. J Clin Microbiol 2014;52:1672–1677 [CrossRef][PubMed]
    [Google Scholar]
  22. Kumari K, Gulati S, Smith DF, Gulati U, Cummings RD et al. Receptor binding specificity of recent human H3N2 influenza viruses. Virol J 2007;4:42 [CrossRef][PubMed]
    [Google Scholar]
  23. Westgeest KB, Bestebroer TM, Spronken MI, Gao J, Couzens L et al. Optimization of an enzyme-linked lectin assay suitable for rapid antigenic characterization of the neuraminidase of human influenza A(H3N2) viruses. J Virol Methods 2015;217:55–63 [CrossRef][PubMed]
    [Google Scholar]
  24. Russell RJ, Haire LF, Stevens DJ, Collins PJ, Lin YP et al. The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 2006;443:45–49 [CrossRef][PubMed]
    [Google Scholar]
  25. Wu Y, Qin G, Gao F, Liu Y, Vavricka CJ et al. Induced opening of influenza virus neuraminidase N2 150-loop suggests an important role in inhibitor binding. Sci Rep 2013;3:1551 [CrossRef][PubMed]
    [Google Scholar]
  26. Taylor NR, von Itzstein M. Molecular modeling studies on ligand binding to sialidase from influenza virus and the mechanism of catalysis. J Med Chem 1994;37:616–624 [CrossRef][PubMed]
    [Google Scholar]
  27. Uhlendorff J, Matrosovich T, Klenk HD, Matrosovich M. Functional significance of the hemadsorption activity of influenza virus neuraminidase and its alteration in pandemic viruses. Arch Virol 2009;154:945–957 [CrossRef][PubMed]
    [Google Scholar]
  28. Laver WG, Colman PM, Webster RG, Hinshaw VS, Air GM. Influenza virus neuraminidase with hemagglutinin activity. Virology 1984;137:314–323 [CrossRef][PubMed]
    [Google Scholar]
  29. Kobasa D, Rodgers ME, Wells K, Kawaoka Y. Neuraminidase hemadsorption activity, conserved in avian influenza A viruses, does not influence viral replication in ducks. J Virol 1997;71:6706–6713[PubMed]
    [Google Scholar]
  30. Hausmann J, Kretzschmar E, Garten W, Klenk HD. N1 neuraminidase of influenza virus A/FPV/Rostock/34 has haemadsorbing activity. J Gen Virol 1995;76:1719–1728 [CrossRef][PubMed]
    [Google Scholar]
  31. Sung JC, van Wynsberghe AW, Amaro RE, Li WW, McCammon JA. Role of secondary sialic acid binding sites in influenza N1 neuraminidase. J Am Chem Soc 2010;132:2883–2885 [CrossRef][PubMed]
    [Google Scholar]
  32. Hooper KA, Bloom JD. A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein. J Virol 2013;87:12531–12540 [CrossRef][PubMed]
    [Google Scholar]
  33. Lee HK, Tang JW, Kong DH, Loh TP, Chiang DK et al. Comparison of mutation patterns in full-genome A/H3N2 influenza sequences obtained directly from clinical samples and the same samples after a single MDCK passage. PLoS One 2013;8:e79252 [CrossRef][PubMed]
    [Google Scholar]
  34. Deyde VM, Sheu TG, Trujillo AA, Okomo-Adhiambo M, Garten R et al. Detection of molecular markers of drug resistance in 2009 pandemic influenza A (H1N1) viruses by pyrosequencing. Antimicrob Agents Chemother 2010;54:1102–1110 [CrossRef][PubMed]
    [Google Scholar]
  35. Okomo-Adhiambo M, Nguyen HT, Sleeman K, Sheu TG, Deyde VM et al. Host cell selection of influenza neuraminidase variants: implications for drug resistance monitoring in A(H1N1) viruses. Antiviral Res 2010;85:381–388 [CrossRef][PubMed]
    [Google Scholar]
  36. Chambers BS, Li Y, Hodinka RL, Hensley SE. Recent H3N2 influenza virus clinical isolates rapidly acquire hemagglutinin or neuraminidase mutations when propagated for antigenic analyses. J Virol 2014;88:10986–10989 [CrossRef][PubMed]
    [Google Scholar]
  37. van Baalen CA, Jeeninga RE, Penders GH, van Gent B, van Beek R et al. ViroSpot microneutralization assay for antigenic characterization of human influenza viruses. Vaccine 2017;35:46–52 [CrossRef][PubMed]
    [Google Scholar]
  38. Lin Y, Gu Y, Wharton SA, Whittaker L, Gregory V et al. Optimization of a micro-neutralisation assay and its application in antigenic characterisation of influenza viruses. Influenza Other Respir Viruses 2015;331–340 [CrossRef][PubMed]
    [Google Scholar]
  39. Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG. A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci USA 2000;97:6108–6113 [CrossRef][PubMed]
    [Google Scholar]
  40. de Wit E, Spronken MI, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD et al. Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments. Virus Res 2004;103:155–161 [CrossRef][PubMed]
    [Google Scholar]
  41. Koel BF, Burke DF, Bestebroer TM, van der Vliet S, Zondag GC et al. Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution. Science 2013;342:976–979 [CrossRef][PubMed]
    [Google Scholar]
  42. Hirst GK. Studies of antigenic differences among strains of influenza A by means of red cell agglutination. J Exp Med 1943;78:407–423 [CrossRef][PubMed]
    [Google Scholar]
  43. Koel BF, Mögling R, Chutinimitkul S, Fraaij PL, Burke DF et al. Identification of amino acid substitutions supporting antigenic change of influenza A(H1N1)pdm09 viruses. J Virol 2015;89:3763–3775 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000809
Loading
/content/journal/jgv/10.1099/jgv.0.000809
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF

Most cited articles

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