Glycosylation of H4 influenza strains with pandemic potential and susceptibilities to lung surfactant SP-D

Lisa M Parsons; Olga Zoueva; Gabrielle Grubbs; Ewan Plant; Ewa Jankowska; Yijia Xie; Hao Song; George F Gao; Zhiping Ye; Surender Khurana; John F Cipollo

doi:10.3389/fmolb.2023.1207670

Glycosylation of H4 influenza strains with pandemic potential and susceptibilities to lung surfactant SP-D

Front Mol Biosci. 2023 Jun 13:10:1207670. doi: 10.3389/fmolb.2023.1207670. eCollection 2023.

Authors

Affiliations

¹ Food and Drug Administration, Center for Biologics Evaluation and Research, Division of Bacterial, Parasitic and Allergenic Products, Silver Spring, MD, United States.
² Food and Drug Administration, Center for Biologics Evaluation and Research, Division of Viral Products, Silver Spring, MD, United States.
³ Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.

Abstract

We recently reported that members of group 1 influenza A virus (IAV) containing H2, H5, H6, and H11 hemagglutinins (HAs) are resistant to lung surfactant protein D (SP-D). H3 viruses, members of group 2 IAV, have high affinity for SP-D, which depends on the presence of high-mannose glycans at glycosite N165 on the head of HA. The low affinity of SP-D for the group 1 viruses is due to the presence of complex glycans at an analogous glycosite on the head of HA, and replacement with high-mannose glycan at this site evoked strong interaction with SP-D. Thus, if members of group 1 IAV were to make the zoonotic leap to humans, the pathogenicity of such strains could be problematic since SP-D, as a first-line innate immunity factor in respiratory tissues, could be ineffective as demonstrated in vitro. Here, we extend these studies to group 2 H4 viruses that are representative of those with specificity for avian or swine sialyl receptors, i.e., those with receptor-binding sites with either Q226 and G228 for avian or recent Q226L and G228S mutations that facilitate swine receptor specificity. The latter have increased pathogenicity potential in humans due to a switch from avian sialylα2,3 to sialylα2,6 glycan receptor preference. A better understanding of the potential action of SP-D against these strains will provide important information regarding the pandemic risk of such strains. Our glycomics and in vitro analyses of four H4 HAs reveal SP-D-favorable glycosylation patterns. Therefore, susceptibilities to this first-line innate immunity defense respiratory surfactant against such H4 viruses are high and align with H3 HA glycosylation.

Keywords: collectin; glycopeptides; glycoproteomics; pathogenicity; reassortment; sialic acid; swine.

Grants and funding

This work was supported by Program/Grant numbers Z01 BJ 02044-13 LBP from the US Food and Drug Administration to JC and the National Science and Technology Major Project (2018ZX10733403) to GFG and HS.