{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:55:10Z","timestamp":1790402110770,"version":"4.1.0"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T00:00:00Z","timestamp":1264982400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Two viruses isolated during the highly pathogenic avian influenza (HPAI) H7N7 virus outbreak in The Netherlands in 2003, one isolated from a person with conjunctivitis and one from a person who died as the result of infection, were used for an\n            <jats:italic>in vitro<\/jats:italic>\n            study of influenza A virus pathogenicity factors. The two HPAI H7N7 viruses differed in 15 amino acid positions in five gene segments. Assays were designed to investigate the role of each of these substitutions in attachment and entry, transcription and genome replication, and virus production and release as determined by hemagglutinin (HA), polymerase proteins, nonstructural protein 1 (NS1), and neuraminidase (NA). These\n            <jats:italic>in vitro<\/jats:italic>\n            studies confirmed the roles of the E627K substitution in basic polymerase 2 (PB2) and the A143T substitution in HA in pathogenicity observed in a mouse model previously. However, the\n            <jats:italic>in vitro<\/jats:italic>\n            studies identified a contribution of acidic polymerase (PA) and NA to the efficient replication in human cells of the fatal case virus, despite the fact that these are rarely marked as determinants of pathogenicity in\n            <jats:italic>in vivo<\/jats:italic>\n            studies. With the exception of PB2 E627K, all substitutions contributing to enhanced replication of the fatal case virus\n            <jats:italic>in vitro<\/jats:italic>\n            were present in poultry viruses prior to transmission to the human fatal case, indicating that viruses with enhanced replication efficiency in the mammalian host can be generated in poultry. Thus, detailed\n            <jats:italic>in vitro<\/jats:italic>\n            analyses of mutations facilitating replication of avian influenza viruses in mammalian cells are important to assess the zoonotic risk posed by these viruses and, in addition, highlight the value of\n            <jats:italic>in vitro<\/jats:italic>\n            studies to complement animal models.\n          <\/jats:p>","DOI":"10.1128\/jvi.01783-09","type":"journal-article","created":{"date-parts":[[2009,11,26]],"date-time":"2009-11-26T05:03:27Z","timestamp":1259211807000},"page":"1597-1606","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":137,"title":["Molecular Determinants of Adaptation of Highly Pathogenic Avian Influenza H7N7 Viruses to Efficient Replication in the Human Host"],"prefix":"10.1128","volume":"84","author":[{"given":"Emmie","family":"de Wit","sequence":"first","affiliation":[{"name":"National Influenza Center and Department of Virology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent J.","family":"Munster","sequence":"additional","affiliation":[{"name":"National Influenza Center and Department of Virology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debby","family":"van Riel","sequence":"additional","affiliation":[{"name":"National Influenza Center and Department of Virology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter E. P.","family":"Beyer","sequence":"additional","affiliation":[{"name":"National Influenza Center and Department of Virology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guus F.","family":"Rimmelzwaan","sequence":"additional","affiliation":[{"name":"National Influenza Center and Department of Virology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thijs","family":"Kuiken","sequence":"additional","affiliation":[{"name":"National Influenza Center and Department of Virology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert D. M. E.","family":"Osterhaus","sequence":"additional","affiliation":[{"name":"National Influenza Center and Department of Virology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron A. 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