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Influenza A/H4N2 mallard infection experiments further indicate zanamivir as less prone to induce environmental resistance development than oseltamivir
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2020 (English)In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 101, no 8, p. 816-824Article in journal (Refereed) Published
Abstract [en]

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 in vivo 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 µg l−1 of ZA in the water environment. Two neuraminidase substitutions emerged, H274N (ZA IC50 increased 5.5-fold) and E119G (ZA IC50 increased 110-fold) at 10 and 100 µg l−1 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.

Place, publisher, year, edition, pages
Microbiology Society , 2020. Vol. 101, no 8, p. 816-824
Keywords [en]
avian influenza, neuraminidase inhibitor, antiviral resistance, pandemic preparedness, drug residues, environment, LPAI, influenza A, zanamivir, H4N2
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:umu:diva-175100DOI: 10.1099/jgv.0.001369ISI: 000563710600006PubMedID: 31855133Scopus ID: 2-s2.0-85090076652OAI: oai:DiVA.org:umu-175100DiVA, id: diva2:1468152
Funder
Swedish Research Council Formas, 211-2013-1320Swedish Research Council Formas, 2016-00790Swedish Research Council, 2016-02606Available from: 2020-09-17 Created: 2020-09-17 Last updated: 2023-03-23Bibliographically approved

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Söderström Lindström, HannaTang, ChaojunLindberg, Richard H.

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Tepper, ViktoriaWille, MichelleSöderström Lindström, HannaTang, ChaojunLindberg, Richard H.Järhult, Josef D.
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Section of Sustainable HealthDepartment of Chemistry
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Journal of General Virology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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