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Other HA traits necessary for pandemic potential are poorly understood. For swine influenza viruses isolated in 2009\u20132016, gamma-clade viruses had less stable HA proteins (activation pH 5.5\u20135.9) than pandemic clade (pH 5.0\u20135.5). Gamma-clade viruses replicated to higher levels in mammalian cells than pandemic clade. In ferrets, a model for human adaptation, a relatively stable HA protein (pH 5.5\u20135.6) was necessary for efficient replication and airborne transmission. The overall airborne transmission frequency in ferrets for four isolates tested was 42%, and isolate G15 airborne transmitted 100% after selection of a variant with a stabilized HA. The results suggest swine influenza viruses containing both a stabilized HA and alpha-2,6 receptor binding in tandem pose greater pandemic risk. Increasing evidence supports adding HA stability to pre-pandemic risk assessment algorithms.<\/jats:p>","DOI":"10.7554\/elife.56236","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T11:00:30Z","timestamp":1593082830000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.56236","source":"Crossref","is-referenced-by-count":23,"title":["HA stabilization promotes replication and transmission of swine H1N1 gamma influenza viruses in ferrets"],"prefix":"10.7554","volume":"9","author":[{"given":"Meng","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guohua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, United 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