N-linked glycosylation attenuates H3N2 influenza viruses

David J. Vigerust, Kimberly B. Ulett, Kelli L. Boyd, Jens Madsen, Samuel Hawgood, Jonathan Mccullers

Research output: Contribution to journalArticle

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Abstract

Over the last four decades, H3N2 subtype influenza A viruses have gradually acquired additional potential sites for glycosylation within the globular head of the hemagglutinin (HA) protein. Here, we have examined the biological effect of additional glycosylation on the virulence of H3N2 influenza viruses. We created otherwise isogenic reassortant viruses by site-directed mutagenesis that contain additional potential sites for glycosylation and examined the effect on virulence in naive BALB/c, C57BL/6, and surfactant protein D (SP-D)-deficient mice. The introduction of additional sites was consistent with the sequence of acquisition in the globular head over the past 40 years, beginning with two sites in 1968 to the seven sites found in contemporary influenza viruses circulating in 2000. Decreased morbidity and mortality, as well as lower viral lung titers, were seen in mice as the level of potential glycosylation of the viruses increased. This correlated with decreased evidence of virus-mediated lung damage and increased in vitro inhibition of hemagglutination by SP-D. SP-D-deficient animals displayed an inverse pattern of disease, such that more highly glycosylated viruses elicited disease equivalent to or exceeding that of the wild type. We conclude from these data that increased glycosylation of influenza viruses results in decreased virulence, which is at least partly mediated by SP-D-induced clearance from the lung. The continued exploration of interactions between highly glycosylated viruses and surfactant proteins may lead to an improved understanding of the biology within the lung and strategies for viral control.

Original languageEnglish (US)
Pages (from-to)8593-8600
Number of pages8
JournalJournal of Virology
Volume81
Issue number16
DOIs
StatePublished - Aug 1 2007

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H3N2 Subtype Influenza A Virus
Pulmonary Surfactant-Associated Protein D
Orthomyxoviridae
glycosylation
Glycosylation
surfactants
viruses
lungs
Virulence
Lung
virulence
Viruses
proteins
Reassortant Viruses
site-directed mutagenesis
mice
Hemagglutination
Hemagglutinins
Virus Diseases
hemagglutinins

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Vigerust, D. J., Ulett, K. B., Boyd, K. L., Madsen, J., Hawgood, S., & Mccullers, J. (2007). N-linked glycosylation attenuates H3N2 influenza viruses. Journal of Virology, 81(16), 8593-8600. https://doi.org/10.1128/JVI.00769-07

N-linked glycosylation attenuates H3N2 influenza viruses. / Vigerust, David J.; Ulett, Kimberly B.; Boyd, Kelli L.; Madsen, Jens; Hawgood, Samuel; Mccullers, Jonathan.

In: Journal of Virology, Vol. 81, No. 16, 01.08.2007, p. 8593-8600.

Research output: Contribution to journalArticle

Vigerust, DJ, Ulett, KB, Boyd, KL, Madsen, J, Hawgood, S & Mccullers, J 2007, 'N-linked glycosylation attenuates H3N2 influenza viruses', Journal of Virology, vol. 81, no. 16, pp. 8593-8600. https://doi.org/10.1128/JVI.00769-07
Vigerust DJ, Ulett KB, Boyd KL, Madsen J, Hawgood S, Mccullers J. N-linked glycosylation attenuates H3N2 influenza viruses. Journal of Virology. 2007 Aug 1;81(16):8593-8600. https://doi.org/10.1128/JVI.00769-07
Vigerust, David J. ; Ulett, Kimberly B. ; Boyd, Kelli L. ; Madsen, Jens ; Hawgood, Samuel ; Mccullers, Jonathan. / N-linked glycosylation attenuates H3N2 influenza viruses. In: Journal of Virology. 2007 ; Vol. 81, No. 16. pp. 8593-8600.
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