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Amino acid substitutions in PB2 protein were shown to influence the pathogenicity and transmissibility of H7N9 following experimental infection of ferrets and mice. In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using <jats:italic>ex vivo<\/jats:italic> organ explant cultures. Recombinant viruses of A\/Shanghai\/2\/2013 (rgH7N9) and its mutants with PB2-K627E, PB2-K627E\u2009+\u2009Q591K and PB2-K627E\u2009+\u2009D701N were generated by plasmid-based reverse genetics. PB2-E627K was essential for efficient replication of rgH7N9 in <jats:italic>ex vivo<\/jats:italic> cultures of human and swine respiratory tracts. Mutant rgPB2-K627E\u2009+\u2009D701N replicated better than rgPB2-K627E in human lung but not as well as rgH7N9 virus. The rgPB2-K627E mutant failed to replicate in human type I-like pneumocytes (ATI) and peripheral blood monocyte-derived macrophages (PM\u03d5) at 37\u2009\u00b0C while the compensatory mutant rgPB2-K627E\u2009+\u2009Q591K and rgPB2-K627E\u2009+\u2009D701N had partly restored replication competence in PM\u03d5. Our results demonstrate that PB2-E627K was important for efficient replication of influenza H7N9 in both human and swine respiratory tracts.<\/jats:p>","DOI":"10.1038\/srep35401","type":"journal-article","created":{"date-parts":[[2016,10,14]],"date-time":"2016-10-14T10:24:50Z","timestamp":1476440690000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Evaluation of the human adaptation of influenza A\/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures"],"prefix":"10.1038","volume":"6","author":[{"given":"Louisa L. 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