N-linked glycosylation attenuates H3N2 influenza viruses.

Vigerust DJ, Ulett KB, Boyd KL, Madsen J, Hawgood S, McCullers JA
J Virol. 2007 81 (16): 8593-600

PMID: 17553891 · PMCID: PMC1951338 · DOI:10.1128/JVI.00769-07

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 naïve 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.

MeSH Terms (16)

Animals Female Glycosylation Hemagglutination, Viral Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza, Human Influenza A Virus, H3N2 Subtype Lung Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Oligosaccharides Pulmonary Surfactant-Associated Protein D Virulence

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