{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:31:12Z","timestamp":1772253072271,"version":"3.50.1"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN272201400007C"],"award-info":[{"award-number":["HHSN272201400007C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AI139063-01A1"],"award-info":[{"award-number":["1R01AI139063-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI127893"],"award-info":[{"award-number":["R01AI127893"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["Research Development Program to the University of Pittsburgh"],"award-info":[{"award-number":["Research Development Program to the University of Pittsburgh"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Airborne transmission of seasonal and pandemic influenza viruses is the reason for their epidemiological success and public health burden in humans. Efficient airborne transmission of the H1N1 influenza virus relies on the receptor specificity and pH of fusion of the surface glycoprotein hemagglutinin (HA). In this study, we examined the role of HA pH of fusion on transmissibility of a cell-culture-adapted H3N2 virus. Mutations in the HA head at positions 78 and 212 of A\/Perth\/16\/2009 (H3N2), which were selected after cell culture adaptation, decreased the acid stability of the virus from pH 5.5 (WT) to pH 5.8 (mutant). In addition, the mutant H3N2 virus replicated to higher titers in cell culture but had reduced airborne transmission in the ferret model. These data demonstrate that, like H1N1 HA, the pH of fusion for H3N2 HA is a determinant of efficient airborne transmission. Surprisingly, noncoding regions of the NA segment can impact the pH of fusion of mutant viruses. Taken together, our data confirm that HA acid stability is an important characteristic of epidemiologically successful human influenza viruses and is influenced by HA\/NA balance.<\/jats:p>","DOI":"10.3390\/v13050719","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T21:25:10Z","timestamp":1619040310000},"page":"719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Valerie","family":"Le Sage","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburg, PA 15219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen A.","family":"Kormuth","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburg, PA 15219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Nturibi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburg, PA 15219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juhye M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"},{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila A.","family":"Frizzell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael M.","family":"Myerburg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-3408","authenticated-orcid":false,"given":"Jesse D.","family":"Bloom","sequence":"additional","affiliation":[{"name":"Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"},{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA"},{"name":"Howard Hughes Medical Institute, Seattle, WA 98103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seema 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