Specific sites of N-linked glycosylation on the hemagglutinin of H1N1 subtype influenza A virus determine sensitivity to inhibitors of the innate immune system and virulence in mice

Abstract

Oligosaccharides on the hemagglutinin (HA) and neuraminidase of influenza Avirus (IAV) are a target for recognition by lectins of the innate immune system, including soluble surfactant protein-D and the macrophage mannose receptor on airway macrophages. Glycans attached to the head of H1 subtype of IAV differ markedly in number and location. A reverse genetic approach was used to define the importance of particular N-glycosylation sites on H1 in determining sensitivity to innate immune defenses and virulence in mice. The HA of A/PR/8/34 (PR8, H1N1) and A/Brazil/11/78 (Brazil, H1N1) express zero and four glycosylation sites on the head of HA, respectively. Site-directed mutagenesis was used t..