{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:18:35Z","timestamp":1792142315496,"version":"4.4.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"31","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010890","name":"CSC | Chinese Government Scholarship","doi-asserted-by":"publisher","award":["201908350116"],"award-info":[{"award-number":["201908350116"]}],"id":[{"id":"10.13039\/501100010890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001732","name":"Danmarks Grundforskningsfond","doi-asserted-by":"publisher","award":["DNRF107L"],"award-info":[{"award-number":["DNRF107L"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>To become established upon zoonotic transfer, influenza A viruses (IAV) need to switch binding from \u201cavian-type\u201d \u03b12-3-linked sialic acid receptors (2-3Sia) to \u201chuman-type\u201d Sia\u03b12-6-linked sialic acid receptors (2-6Sia). For the 1968 H3N2 pandemic virus, this was accomplished by two canonical amino acid substitutions in its hemagglutinin (HA) although a full specificity shift had not occurred. The receptor repertoire on epithelial cells is highly diverse and simultaneous interaction of a virus particle with a range of low- to very low-affinity receptors results in tight heteromultivalent binding. How this range of affinities determines binding selectivity and virus motility remains largely unknown as the analysis of low-affinity monovalent HA\u2013receptor interactions is technically challenging. Here, a biolayer interferometry assay enabled a comprehensive analysis of receptor-binding kinetics evolution upon host-switching. Virus-binding kinetics of H3N2 virus isolates slowly evolved from 1968 to 1979 from mixed 2-3\/2-6Sia specificity to high 2-6Sia specificity, surprisingly followed by a decline in selectivity after 1992. By using genetically tuned HEK293 cells, presenting either a simplified 2-3Sia- or 2-6Sia-specific receptor repertoire, receptor-specific binding was shown to correlate strongly with receptor-specific entry. In conclusion, the slow and continuous evolution of entry and receptor-binding specificity of seasonal H3N2 viruses contrasts with the paradigm that human IAVs need to rapidly acquire and maintain a high specificity for 2-6Sia. Analysis of the kinetic parameters of receptor binding provides a basis for understanding virus-binding specificity, motility, and HA\/neuraminidase balance at the molecular level.<\/jats:p>","DOI":"10.1073\/pnas.2304992120","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T13:39:08Z","timestamp":1689773948000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":26,"title":["H3N2 influenza A virus gradually adapts to human-type receptor binding and entry specificity after the start of the 1968 pandemic"],"prefix":"10.1073","volume":"120","author":[{"given":"Mengying","family":"Liu","sequence":"first","affiliation":[{"name":"Virology section, Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0244-0979","authenticated-orcid":false,"given":"A. 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