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糖基工程化的 MDCK 细胞展示了 H3N2 流感的首选受体，而这些受体在用于疫苗的鸡蛋中不存在。

Glyco-engineered MDCK cells display preferred receptors of H3N2 influenza absent in eggs used for vaccines.

机构信息

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.

出版信息

Nat Commun. 2023 Oct 4;14(1):6178. doi: 10.1038/s41467-023-41908-0.

DOI:10.1038/s41467-023-41908-0
PMID:37794004
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10551000/
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.

摘要

人类 H3N2 流感病毒的进化受到免疫选择的驱动，其血凝素 (HA) 的受体特异性已经变窄，只能识别人类型（Neu5Acα2-6Gal）糖受体中的一个受限子集，这些受体具有延伸的多聚-LacNAc（Galβ1-4GlcNAc）重复序列。这种改变的特异性给血凝检测、在实验室宿主中的生长以及在鸡蛋中生产疫苗带来了挑战。为了评估延伸糖受体对病毒结合、感染和生长的影响，我们通过在 MDCK、SIAT 和 hCK 细胞系中过表达β3-N-乙酰氨基葡萄糖基转移酶 2 ，构建了 N-糖延伸 (NExt) 细胞系。在这些细胞系中，SIAT-NExt 细胞表现出对 H3 HA 的显著增强结合和对近期 H3N2 病毒株的易感性，但不影响最终病毒滴度。对这些细胞系以及羊水和鸡胚卵膜的糖组分析提供了对延伸糖受体对近期 H3N2 病毒生长的重要性的深入了解，以及对它们在细胞和基于鸡蛋的疫苗生产中的相关性的深入了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/9897db364e6e/41467_2023_41908_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/b0b3f812171e/41467_2023_41908_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/5942bd1e5300/41467_2023_41908_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/252df96c91c4/41467_2023_41908_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/896668ece46b/41467_2023_41908_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/9897db364e6e/41467_2023_41908_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/b0b3f812171e/41467_2023_41908_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/5942bd1e5300/41467_2023_41908_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/252df96c91c4/41467_2023_41908_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/896668ece46b/41467_2023_41908_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1242/10551000/9897db364e6e/41467_2023_41908_Fig5_HTML.jpg

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