Glycosylation of the hemagglutinin modulates the sensitivity of H3N2 influenza viruses to innate proteins in airway secretions and virulence in mice

Abstract

Collectins in airway fluids and membrane-associated lectins such as the macrophage mannose receptor (MMR) recognize mannose-rich glycans on the envelope glycoproteins of influenza A viruses. In this study, we used a reverse genetic approach to examine the role of particular N-linked glycosylation sites on the hemagglutinin (HA) of A/Beijing/353/89 (Beij/89, H3N2) in determining sensitivity to lectin-mediated immune defenses and virulence in mice. We generated 7:1 reassortant viruses on an A/PR/8/34 backbone with Beij/89 HA or HA lacking one or more glycosylation sites. Asn165 was an important determinant of sensitivity to mouse collectins and virulence but did not alter susceptibility of air..