Lack of transmission of a human influenza virus with avian receptor specificity between ferrets is not due to decreased virus shedding but rather a lower infectivity Free

Abstract

Influenza virus attaches to host cells by sialic acid (SA). Human influenza viruses show preferential affinity for α2,6-linked SA, whereas avian influenza viruses bind α2,3-linked SA. In this study, mutation of the haemagglutinin receptor-binding site of a human H3N2 influenza A virus to switch binding to α2,3-linked SA did not eliminate infection of ferrets but prevented transmission, even in a co-housed model. The mutant virus was shed from the noses of ferrets directly inoculated with virus in the same amounts and for the same length of time as wild-type virus. Mutant virus infection was localized to the same anatomical regions of the upper respiratory tract of directly inoculated animals. Interestingly, wild-type virus was more readily neutralized than the mutant virus by ferret nasal washes containing mucus. Moreover after inoculation of equal doses, the mutant virus grew poorly in ferret nasal turbinate tissue compared with wild-type virus. The dose of mutant virus required to establish infection in the directly inoculated ferrets was 40-fold higher than for wild-type virus. It was concluded that minimum infectious dose is a predictor of virus transmissibility and it is suggested that, as virus passes from one host to another through stringent environmental conditions, viruses with a preference for α2,3-linked SA are unlikely to inoculate a new mammalian host in sufficient quantities to initiate a productive infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.031203-0
2011-08-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/8/1822.html?itemId=/content/journal/jgv/10.1099/vir.0.031203-0&mimeType=html&fmt=ahah

References

  1. Belser J. A., Blixt O., Chen L.-M., Pappas C., Maines T. R., Van Hoeven N., Donis R., Busch J., McBride R. et al. 2008; Contemporary North American influenza H7 viruses possess human receptor specificity: implications for virus transmissibility. Proc Natl Acad Sci U S A 105:7558–7563 [View Article][PubMed]
    [Google Scholar]
  2. Bouvier N. M., Lowen A. C., Palese P. 2008; Oseltamivir-resistant influenza A viruses are transmitted efficiently among guinea pigs by direct contact but not by aerosol. J Virol 82:10052–10058 [View Article][PubMed]
    [Google Scholar]
  3. Connor R. J., Kawaoka Y., Webster R. G., Paulson J. C. 1994; Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 205:17–23 [View Article][PubMed]
    [Google Scholar]
  4. Couceiro J. N. S. S., Paulson J. C., Baum L. G. 1993; Influenza virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium; the role of the host cell in selection of hemagglutinin receptor specificity. Virus Res 29:155–165 [View Article][PubMed]
    [Google Scholar]
  5. de Jong M. D., Simmons C. P., Thanh T. T., Hien V. M., Smith G. J., Chau T. N., Hoang D. M., Chau N. V., Khanh T. H. et al. 2006; Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 12:1203–1207 [View Article][PubMed]
    [Google Scholar]
  6. Duan S., Boltz D. A., Seiler P., Li J., Bragstad K., Nielsen L. P., Webby R. J., Webster R. G., Govorkova E. A. 2010; Oseltamivir-resistant pandemic H1N1/2009 influenza virus possesses lower transmissibility and fitness in ferrets. PLoS Pathog 6:e1001022 [View Article][PubMed]
    [Google Scholar]
  7. Elleman C. J., Barclay W. S. 2004; The M1 matrix protein controls the filamentous phenotype of influenza A virus. Virology 321:144–153 [View Article][PubMed]
    [Google Scholar]
  8. Ha Y., Stevens D. J., Skehel J. J., Wiley D. C. 2003; X-ray structure of the hemagglutinin of a potential H3 avian progenitor of the 1968 Hong Kong pandemic influenza virus. Virology 309:209–218 [View Article][PubMed]
    [Google Scholar]
  9. Kesimer M., Scull M., Brighton B., DeMaria G., Burns K., O’Neal W., Pickles R. J., Sheehan J. K. 2009; Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense. FASEB J 23:1858–1868 [View Article][PubMed]
    [Google Scholar]
  10. Kirkeby S., Martel C. J., Aasted B. 2009; Infection with human H1N1 influenza virus affects the expression of sialic acids of metaplastic mucous cells in the ferret airways. Virus Res 144:225–232 [View Article][PubMed]
    [Google Scholar]
  11. Lai S. K., Wang Y.-Y., Wirtz D., Hanes J. 2009; Micro- and macrorheology of mucus. Adv Drug Deliv Rev 61:86–100 [View Article][PubMed]
    [Google Scholar]
  12. Leigh M. W., Connor R. J., Kelm S., Baum L. G., Paulson J. C. 1995; Receptor specificity of influenza virus influences severity of illness in ferrets. Vaccine 13:1468–1473 [View Article][PubMed]
    [Google Scholar]
  13. Maines T. R., Chen L.-M., Matsuoka Y., Chen H., Rowe T., Ortin J., Falcón A., Nguyen T. H., Mai Q. et al. 2006; Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc Natl Acad Sci U S A 103:12121–12126 [View Article][PubMed]
    [Google Scholar]
  14. Matrosovich M., Klenk H.-D. 2003; Natural and synthetic sialic acid-containing inhibitors of influenza virus receptor binding. Rev Med Virol 13:85–97 [View Article][PubMed]
    [Google Scholar]
  15. Matrosovich M. N., Gambaryan A. S., Teneberg S., Piskarev V. E., Yamnikova S. S., Lvov D. K., Robertson J. S., Karlsson K.-A. 1997; Avian influenza A viruses differ from human viruses by recognition of sialyloligosaccharides and gangliosides and by a higher conservation of the HA receptor-binding site. Virology 233:224–234 [View Article][PubMed]
    [Google Scholar]
  16. Matrosovich M., Tuzikov A., Bovin N., Gambaryan A., Klimov A., Castrucci M. R., Donatelli I., Kawaoka Y. 2000; Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol 74:8502–8512 [View Article][PubMed]
    [Google Scholar]
  17. Matrosovich M. N., Matrosovich T. Y., Gray T., Roberts N. A., Klenk H.-D. 2004; Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proc Natl Acad Sci U S A 101:4620–4624 [View Article][PubMed]
    [Google Scholar]
  18. Matrosovich M., Matrosovich T., Uhlendorff J., Garten W., Klenk H.-D. 2007; Avian-virus-like receptor specificity of the hemagglutinin impedes influenza virus replication in cultures of human airway epithelium. Virology 361:384–390 [View Article][PubMed]
    [Google Scholar]
  19. Matsuoka Y., Lamirande E. W., Subbarao K. 2009; The ferret model for influenza. Curr Protoc Microbiol 13:15G.2.1–15G.2.29[PubMed]
    [Google Scholar]
  20. Mubareka S., Lowen A. C., Steel J., Coates A. L., García-Sastre A., Palese P. 2009; Transmission of influenza virus via aerosols and fomites in the guinea pig model. J Infect Dis 199:858–865 [View Article][PubMed]
    [Google Scholar]
  21. Naeve C. W., Hinshaw V. S., Webster R. G. 1984; Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus. J Virol 51:567–569[PubMed]
    [Google Scholar]
  22. Neumann G., Watanabe T., Ito H., Watanabe S., Goto H., Gao P., Hughes M., Perez D. R., Donis R. et al. 1999; Generation of influenza A viruses entirely from cloned cDNAs. Proc Natl Acad Sci U S A 96:9345–9350 [View Article][PubMed]
    [Google Scholar]
  23. Pappas C., Viswanathan K., Chandrasekaran A., Raman R., Katz J. M., Sasisekharan R., Tumpey T. M. 2010; Receptor specificity and transmission of H2N2 subtype viruses isolated from the pandemic of 1957. PLoS ONE 5:e11158 [View Article][PubMed]
    [Google Scholar]
  24. Scull M. A., Gillim-Ross L., Santos C., Roberts K. L., Bordonali E., Subbarao K., Barclay W. S., Pickles R. J. 2009; Avian influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways. PLoS Pathog 5:e1000424 [View Article][PubMed]
    [Google Scholar]
  25. Shelton H., Ayora-Talavera G., Ren J., Loureiro S., Pickles R. J., Barclay W. S., Jones I. M. 2011; Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential. J Virol 85:1875–1880 [View Article][PubMed]
    [Google Scholar]
  26. Shinya K., Ebina M., Yamada S., Ono M., Kasai N., Kawaoka Y. 2006; Avian flu: influenza virus receptors in the human airway. Nature 440:435–436 [View Article][PubMed]
    [Google Scholar]
  27. Song H., Wan H., Araya Y., Perez D. R. 2009; Partial direct contact transmission in ferrets of a mallard H7N3 influenza virus with typical avian-like receptor specificity. Virol J 6:126 [View Article][PubMed]
    [Google Scholar]
  28. Sorrell E. M., Wan H., Araya Y., Song H., Perez D. R. 2009; Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proc Natl Acad Sci U S A 106:7565–7570 [View Article][PubMed]
    [Google Scholar]
  29. Steel J., Lowen A. C., Mubareka S., Palese P. 2009; Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog 5:e1000252 [View Article][PubMed]
    [Google Scholar]
  30. Steel J., Staeheli P., Mubareka S., García-Sastre A., Palese P., Lowen A. C. 2010; Transmission of pandemic H1N1 influenza virus and impact of prior exposure to seasonal strains or interferon treatment. J Virol 84:21–26 [View Article][PubMed]
    [Google Scholar]
  31. Taubenberger J. K., Morens D. M. 2010; Influenza: the once and future pandemic. Public Health Rep 125:Suppl. 316–26[PubMed]
    [Google Scholar]
  32. Tellier R. 2009; Aerosol transmission of influenza A virus: a review of new studies. J R Soc Interface 6:Suppl. 6S783–S790 [View Article][PubMed]
    [Google Scholar]
  33. Thomas Y., Vogel G., Wunderli W., Suter P., Witschi M., Koch D., Tapparel C., Kaiser L. 2008; Survival of influenza virus on banknotes. Appl Environ Microbiol 74:3002–3007 [View Article][PubMed]
    [Google Scholar]
  34. Thompson C. I., Barclay W. S., Zambon M. C., Pickles R. J. 2006; Infection of human airway epithelium by human and avian strains of influenza A virus. J Virol 80:8060–8068 [View Article][PubMed]
    [Google Scholar]
  35. Tumpey T. M., Maines T. R., Van Hoeven N., Glaser L., Solórzano A., Pappas C., Cox N. J., Swayne D. E., Palese P. et al. 2007; A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science 315:655–659 [View Article][PubMed]
    [Google Scholar]
  36. Van Hoeven N., Pappas C., Belser J. A., Maines T. R., Zeng H., García-Sastre A., Sasisekharan R., Katz J. M., Tumpey T. M. 2009; Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air. Proc Natl Acad Sci U S A 106:3366–3371 [View Article][PubMed]
    [Google Scholar]
  37. van Riel D., Munster V. J., de Wit E., Rimmelzwaan G. F., Fouchier R. A., Osterhaus A. D., Kuiken T. 2006; H5N1 virus attachment to lower respiratory tract. Science 312:399 [View Article][PubMed]
    [Google Scholar]
  38. van Riel D., Munster V. J., de Wit E., Rimmelzwaan G. F., Fouchier R. A., Osterhaus A. D., Kuiken T. 2007; Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals. Am J Pathol 171:1215–1223 [View Article][PubMed]
    [Google Scholar]
  39. Wan H., Sorrell E. M., Song H., Hossain M. J., Ramirez-Nieto G., Monne I., Stevens J., Cattoli G., Capua I. et al. 2008; Replication and transmission of H9N2 influenza viruses in ferrets: evaluation of pandemic potential. PLoS ONE 3:e2923 [View Article][PubMed]
    [Google Scholar]
  40. Xu Q., Wang W., Cheng X., Zengel J., Jin H. 2010; Influenza H1N1 A/Solomon Island/3/06 virus receptor binding specificity correlates with virus pathogenicity, antigenicity, and immunogenicity in ferrets. J Virol 84:4936–4945 [View Article][PubMed]
    [Google Scholar]
  41. Yen H.-L., Lipatov A. S., Ilyushina N. A., Govorkova E. A., Franks J., Yilmaz N., Douglas A., Hay A., Krauss S. et al. 2007; Inefficient transmission of H5N1 influenza viruses in a ferret contact model. J Virol 81:6890–6898 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.031203-0
Loading
/content/journal/jgv/10.1099/vir.0.031203-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed