{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:51:09Z","timestamp":1791975069438,"version":"4.4.0"},"reference-count":72,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"unspecified","delay-in-days":286,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Anim. Health. Res. Rev."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The adaptive evolution of influenza A virus is strongly influenced by the functional balance between its two major surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Although previous studies have demonstrated the importance of HA\/NA interplay in receptor binding, virion release, cross-host transmission, and antiviral resistance, most have focused on individual proteins, specific residues, or discrete stages of infection. Consequently, how HA\/NA functional balance responds to selective pressures and contributes to viral adaptive evolution remains incompletely understood. Here, we propose a dynamic \u2018balance\u2013imbalance\u2013rebalance\u2019 framework centred on the coordination between HA-mediated receptor binding and NA-mediated receptor cleavage. We systematically examine how HA\/NA functional balance influences viral attachment, release, and transmission, cross-species adaptation, pathogenicity, immune escape, and antiviral resistance. We further discuss how changes in receptor availability, immune pressure, and antiviral selection may disrupt a pre-existing HA\/NA balance and how coordinated changes in HA and NA may compensate for these perturbations to establish new adaptive states. Future studies integrating structural biology, virology, animal models, and large-scale evolutionary analyses will be essential for quantitatively defining the molecular principles and adaptive boundaries of HA\/NA coevolution, thereby improving our ability to assess the evolutionary potential and cross-host transmission risk of emerging influenza viruses.<\/jats:p>","DOI":"10.1017\/s1466252326100188","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:19:05Z","timestamp":1791973145000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["Functional balance between hemagglutinin and neuraminidase shapes the adaptive evolution of influenza A virus"],"prefix":"10.1017","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-7437","authenticated-orcid":false,"given":"Yanting","family":"Zhu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"Jilin University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peige","family":"Cao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"Jilin University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixue","family":"Sun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02an57k10","id-type":"ROR","asserted-by":"publisher"}],"name":"Changchun 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Published by Cambridge University Press.","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"e6"}}