{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:10:13Z","timestamp":1790061013374,"version":"4.0.1"},"reference-count":41,"publisher":"Microbiology Society","issue":"8","funder":[{"name":"Svenska Forskningsr\u00e5det Formas","award":["2016-00790"],"award-info":[{"award-number":["2016-00790"]}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"crossref","award":["2016-02606"],"award-info":[{"award-number":["2016-02606"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:p>Neuraminidase inhibitors (NAIs) are the gold standard treatment for influenza A virus (IAV). Oseltamivir is mostly used, followed by zanamivir (ZA). NAIs are not readily degraded in conventional wastewater treatment plants and can be detected in aquatic environments. Waterfowl are natural IAV hosts and replicating IAVs could thus be exposed to NAIs in the environment and develop resistance. Avian IAVs form the genetic basis for new human IAVs, and a resistant IAV with pandemic potential poses a serious public health threat, as NAIs constitute a pandemic preparedness cornerstone. Resistance development in waterfowl IAVs exposed to NAIs in the water environment has previously been investigated in an <jats:italic>in vivo<\/jats:italic> mallard model and resistance development was demonstrated in several avian IAVs after the exposure of infected ducks to oseltamivir, and in an H1N1 IAV after exposure to ZA. The N1 and N2 types of IAVs have different characteristics and resistance mutations, and so the present study investigated the exposure of an N2-type IAV (H4N2) in infected mallards to 1, 10 and 100\u2009\u00b5g l<jats:sup>\u22121<\/jats:sup> of ZA in the water environment. Two neuraminidase substitutions emerged, H274N (ZA IC<jats:sub>50<\/jats:sub> increased 5.5-fold) and E119G (ZA IC<jats:sub>50<\/jats:sub> increased 110-fold) at 10 and 100\u2009\u00b5g l<jats:sup>\u22121<\/jats:sup> of ZA, respectively. Reversion towards wild-type was observed for both substitutions in experiments with removed drug pressure, indicating reduced fitness of both resistant viruses. These results corroborate previous findings that the development of resistance to ZA in the environment seems less likely to occur than the development of resistance to oseltamivir, adding information that is useful in planning for prudent drug use and pandemic preparedness.<\/jats:p>","DOI":"10.1099\/jgv.0.001369","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T17:14:58Z","timestamp":1576775698000},"page":"816-824","source":"Crossref","is-referenced-by-count":9,"title":["Influenza A\/H4N2 mallard infection experiments further indicate zanamivir as less prone to induce environmental resistance development than oseltamivir"],"prefix":"10.1099","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6702-7617","authenticated-orcid":false,"given":"Viktoria","family":"Tepper","sequence":"first","affiliation":[{"name":"Institute of Environmental Engineering, ETH Z\u00fcrich, Switzerland"},{"name":"Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Nykvist","sequence":"additional","affiliation":[{"name":"Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gillman","sequence":"additional","affiliation":[{"name":"Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Skog","sequence":"additional","affiliation":[{"name":"Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5629-0196","authenticated-orcid":false,"given":"Michelle","family":"Wille","sequence":"additional","affiliation":[{"name":"Present address: WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia"},{"name":"Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna S\u00f6derstr\u00f6m","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Lindberg","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5ke","family":"Lundkvist","sequence":"additional","affiliation":[{"name":"Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7075-1059","authenticated-orcid":false,"given":"Josef D.","family":"J\u00e4rhult","sequence":"additional","affiliation":[{"name":"Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1122438"},{"key":"R2","first-page":"697 p","volume-title":"Textbook of Influenza","author":"Webster","year":"2014"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2013.0990"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.7589\/0090-3558-47.2.401"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2017.08.004"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-2659.2011.00304.x"},{"key":"R7","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.3201\/eid1510.090844","article-title":"Maximizing the value of drug stockpiles for pandemic influenza","volume":"15","author":"ALW","year":"2009","journal-title":"Emerg Infect Dis"},{"key":"R8","article-title":"A Study of Intravenous Zanamivir in the Treatment of Hospitalized Patients With Influenza Infection - 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