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Cell lines can also differ in the presence of virus receptors, such as the sialic acid (Sia) receptors used by influenza A viruses (IAV), which can vary in linkage (\u03b12,3\u2010 or \u03b12,6\u2010linkage) and form (<jats:italic>N<\/jats:italic>\u2010glycolylneuraminic acid [Neu5Gc] or <jats:italic>N<\/jats:italic>\u2010acetylneuraminic acid [Neu5Ac]). The selective pressures resulting from passaging viruses in cell types with host\u2010specific variations in viral receptors are still only partially understood. IAV are commonly cultured in MDCK cells which are both derived from canine kidney tubule epithelium and inherently heterogeneous. MDCK cells naturally present Neu5Ac and \u03b12,3\u2010linked Sia forms. Here, we examine natural MDCK variant lineages, as well as engineered variants that synthesize Neu5Gc and\/or \u03b12,6\u2010linkages. We determined how viral genetic variation occurred within human H3N2, H1N1 pandemic and canine H3N2 IAV populations when serially passaged in MDCK cell lines that vary in cell type (MDCK\u2010Type I or MDCK\u2010Type II clones) and in Sia display. Deep sequencing of viral genomes showed small numbers of consensus\u2010level mutations, mostly within the hemagglutinin (HA) gene. Both human IAV showed variants in the HA stem and the HA receptor\u2010binding site of populations passaged in cells displaying Neu5Gc. Canine H3N2 showed variants near the receptor\u2010binding site when passaged in cells displaying Neu5Gc or \u03b12,6\u2010linkages. Viruses replicated to low titres in MDCK\u2010Type II cells, suggesting that not all cell types in heterogeneous MDCK cell populations are equally permissive to infection.<\/jats:p>","DOI":"10.1111\/jeb.13890","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T10:35:40Z","timestamp":1623407740000},"page":"1878-1900","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sequence dynamics of three influenza A virus strains grown in different MDCK cell lines, including those expressing different sialic acid receptors"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6283-4543","authenticated-orcid":false,"given":"Karen N.","family":"Barnard","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology College of Veterinary Medicine Baker Institute for Animal Health Cornell University Ithaca NY USA"},{"name":"Fred Hutchinson Cancer Research Center Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5442-3883","authenticated-orcid":false,"given":"Brian R.","family":"Wasik","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Veterinary Medicine Baker Institute for Animal Health Cornell University Ithaca NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4457-0684","authenticated-orcid":false,"given":"Brynn K.","family":"Alford","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Veterinary Medicine Baker Institute for Animal Health Cornell University Ithaca NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6213-5013","authenticated-orcid":false,"given":"Jessica J.","family":"Hayward","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences College of Veterinary Medicine Cornell University Ithaca NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1726-8049","authenticated-orcid":false,"given":"Wendy S.","family":"Weichert","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Veterinary Medicine Baker Institute for Animal Health Cornell University Ithaca NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3189-1101","authenticated-orcid":false,"given":"Ian E. H.","family":"Voorhees","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Veterinary Medicine Baker Institute for Animal Health Cornell University Ithaca NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9596-3552","authenticated-orcid":false,"given":"Edward C.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Marie Bashir Institute for Infectious Diseases and Biosecurity Charles Perkins Centre School of Biological Sciences and School of Medical Sciences University of Sydney Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1836-6655","authenticated-orcid":false,"given":"Colin R.","family":"Parrish","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Veterinary Medicine Baker Institute for Animal Health Cornell University Ithaca NY 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