Glyco-engineered MDCK cells display preferred receptors of H3N2 influenza absent in eggs used for vaccines
File(s)s41467-023-41908-0.pdf (1.8 MB)
Published version
Author(s)
Type
Journal Article
Abstract
Evolution of human H3N2 influenza viruses driven by immune selection has narrowed the receptor specificity of the hemagglutinin (HA) to a restricted subset of human-type (Neu5Acα2-6 Gal) glycan receptors that have extended poly-LacNAc (Galβ1-4GlcNAc) repeats. This altered specificity has presented challenges for hemagglutination assays, growth in laboratory hosts, and vaccine production in eggs. To assess the impact of extended glycan receptors on virus binding, infection, and growth, we have engineered N-glycan extended (NExt) cell lines by overexpressing β3-Ν-acetylglucosaminyltransferase 2 in MDCK, SIAT, and hCK cell lines. Of these, SIAT-NExt cells exhibit markedly increased binding of H3 HAs and susceptibility to infection by recent H3N2 virus strains, but without impacting final virus titers. Glycome analysis of these cell lines and allantoic and amniotic egg membranes provide insights into the importance of extended glycan receptors for growth of recent H3N2 viruses and relevance to their production for cell- and egg-based vaccines.
Date Issued
2023-10-04
Date Acceptance
2023-09-15
Citation
Nature Communications, 2023, 14 (1)
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Volume
14
Issue
1
Copyright Statement
© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37794004
PII: 10.1038/s41467-023-41908-0
Subjects
Animals
Dogs
Hemagglutinin Glycoproteins, Influenza Virus
Humans
Influenza A Virus, H3N2 Subtype
Influenza Vaccines
Influenza, Human
Madin Darby Canine Kidney Cells
Polysaccharides
Publication Status
Published
Coverage Spatial
England
Article Number
ARTN 6178