Lectin-mediated binding and sialoglycans of porcine surfactant protein D synergistically neutralize influenza A virus

The Journal of Biological Chemistry
Martin van EijkHenk P Haagsman

Abstract

Innate immunity is critical in the early containment of influenza A virus (IAV) infection, and surfactant protein D (SP-D) plays a crucial role in the pulmonary defense against IAV. In pigs, which are important intermediate hosts during the generation of pandemic IAVs, SP-D uses its unique carbohydrate recognition domain (CRD) to interact with IAV. An N-linked CRD glycosylation provides interactions with the sialic acid-binding site of IAV, and a tripeptide loop at the lectin-binding site facilitates enhanced interactions with IAV glycans. Here, to investigate both mechanisms of IAV neutralization in greater detail, we produced an N-glycosylated neck-CRD fragment of porcine SP-D (RpNCRD) in HEK293 cells. X-ray crystallography disclosed that the N-glycan did not alter the CRD backbone structure, including the lectin site conformation, but revealed a potential second nonlectin-binding site for glycans. IAV hemagglutination inhibition, IAV aggregation, and neutralization of IAV infection studies showed that RpNCRD, unlike the human analogue RhNCRD, exhibits potent neutralizing activity against pandemic A/Aichi/68 (H3N2), enabled by both porcine-specific structural features of its CRD. MS analysis revealed an N-glycan site-occupanc...Continue Reading

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Citations

Oct 13, 2019·Molecular & Cellular Proteomics : MCP·Deborah Chang, Joseph Zaia
Dec 16, 2018·Bioscience Reports·Ian A YorkIrina V Alymova
Dec 1, 2019·Molecular & Cellular Proteomics : MCP·Deborah Chang, Joseph Zaia
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Kevan L Hartshorn
Mar 25, 2021·Current Protocols·Meizhe WangJoseph Zaia

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