{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:50:41Z","timestamp":1761598241919,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T00:00:00Z","timestamp":1595548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007652","name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria","doi-asserted-by":"publisher","award":["RTA 2011-00111-C03"],"award-info":[{"award-number":["RTA 2011-00111-C03"]}],"id":[{"id":"10.13039\/100007652","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["GR09\/0023, GR09\/0040, GR09\/0039"],"award-info":[{"award-number":["GR09\/0023, GR09\/0040, GR09\/0039"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Oseltamivir is a common therapy against influenza A virus (IAV) infections. The acquisition of oseltamivir resistance (OR) mutations, such as H275Y, hampers viral fitness. However, OR H1N1 viruses have demonstrated the ability to spread throughout different populations. The objective of this work was to compare the fitness of two strains of OR (R6 and R7) containing the H275Y mutation, and a wild-type (F) pandemic influenza A (H1N1) 2009 (pdm09) virus both in vitro and in vivo in mice and to select one OR strain for a comparison with F in ferrets. R6 showed faster replication and pathogenicity than R7 in vitro and in mice. Subsequently, R6 was selected for the fitness comparison with the F strain in ferrets. Ferrets infected with the F virus showed more severe clinical signs, histopathological lung lesions, and viral quantification when compared to OR R6-infected animals. More importantly, differential viral kinetics correlated with differential pro-inflammatory host immune responses in the lungs of infected ferrets, where OR-infected animals developed a protective higher expression of type I IFN and Retinoid acid Inducible Gene I (RIG-I) genes early after infection, resulting in the development of milder disease. These results suggest the presence of early specific viral-host immune interactions relevant in the development of influenza-associated lung pathology.<\/jats:p>","DOI":"10.3390\/v12080794","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T09:06:09Z","timestamp":1595581569000},"page":"794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1724-1006","authenticated-orcid":false,"given":"Beatriz","family":"Vida\u00f1a","sequence":"first","affiliation":[{"name":"Bristol Veterinary School, Faculty of Health Sciences, University of Bristol, Langford, Bristol BS40 5DU, UK"},{"name":"IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Espa\u00f1a"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Mart\u00ednez-Orellana","sequence":"additional","affiliation":[{"name":"IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Espa\u00f1a"},{"name":"Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Martorell","sequence":"additional","affiliation":[{"name":"Departament de Medicina i Cirurgia Animals, Facultat de Veterinaria, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5990-4045","authenticated-orcid":false,"given":"Massimiliano","family":"Baratelli","sequence":"additional","affiliation":[{"name":"IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Espa\u00f1a"},{"name":"HIPRA Laboratories, Avda. la Selva 135, 17170 Amer (Girona), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Espa\u00f1a"},{"name":"Departament de Sanitat i d\u2019Anatomia Animals, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2935-928X","authenticated-orcid":false,"given":"Lourdes","family":"Migura-Garcia","sequence":"additional","affiliation":[{"name":"IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Espa\u00f1a"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"C\u00f3rdoba","sequence":"additional","affiliation":[{"name":"IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Espa\u00f1a"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Espa\u00f1a"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inmaculada","family":"Casas","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III (ISCIII), 28220 Majadahonda, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1828-733X","authenticated-orcid":false,"given":"Francisco","family":"Pozo","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III (ISCIII), 28220 Majadahonda, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8980-5862","authenticated-orcid":false,"given":"Lorenzo","family":"Fraile","sequence":"additional","affiliation":[{"name":"Department de Ci\u00e8ncia Animal, Universitat de Lleida, 25198 Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nat\u00e0lia","family":"Maj\u00f3","sequence":"additional","affiliation":[{"name":"IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Espa\u00f1a"},{"name":"Departament de Sanitat i d\u2019Anatomia Animals, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5703-7360","authenticated-orcid":false,"given":"Mar\u00eda","family":"Montoya","sequence":"additional","affiliation":[{"name":"IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Espa\u00f1a"},{"name":"Centro de Investigaciones Biol\u00f3gicas Margarita Salas (CIB-CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"b5213","DOI":"10.1136\/bmj.b5213","article-title":"Mortality from pandemic A\/H1N1 2009 influenza in England: Public health surveillance study","volume":"339","author":"Donaldson","year":"2009","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nature08182","article-title":"Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic","volume":"459","author":"Smith","year":"2009","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1099\/vir.2008.007260-0","article-title":"High prevalence of amantadine resistance among circulating European porcine influenza A viruses","volume":"90","author":"Krumbholz","year":"2009","journal-title":"J. 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