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Antiviral susceptibility of avian and swine influenza virus of the N1 neuraminidase subtype.

Abstract

Influenza viruses of the N1 neuraminidase (NA) subtype affecting both animals and humans caused the 2009 pandemic. Anti-influenza virus NA inhibitors are crucial early in a pandemic, when specific influenza vaccines are unavailable. Thus, it is urgent to confirm the antiviral susceptibility of the avian viruses, a potential source of a pandemic virus. We evaluated the NA inhibitor susceptibilities of viruses of the N1 subtype isolated from wild waterbirds, swine, and humans. Most avian viruses were highly or moderately susceptible to oseltamivir (50% inhibitory concentration [IC(50)], <5.1 to 50 nM). Of 91 avian isolates, 7 (7.7%) had reduced susceptibility (IC(50), >50 nM) but were sensitive to the NA inhibitors zanamivir and peramivir. Oseltamivir susceptibility ranged more widely among the waterbird viruses (IC(50), 0.5 to 154.43 nM) than among swine and human viruses (IC(50), 0.33 to 2.56 nM). Swine viruses were sensitive to oseltamivir, compared to human seasonal H1N1 isolated before 2007 (mean IC(50), 1.4 nM). Avian viruses from 2007 to 2008 were sensitive to oseltamivir, in contrast to the emergence of resistant H1N1 in humans. Susceptibility remained high to moderate over time among influenza viruses. Sequence analysis of the outliers did not detect molecular markers of drug-resistance (e.g., H275Y NA mutation [N1 numbering]) but revealed mutations outside the NA active site. In particular, V267I, N307D, and V321I residue changes were found, and structural analyses suggest that these mutations distort hydrophobic pockets and affect residues in the NA active site. We determined that natural oseltamivir resistance among swine and wild waterbirds is rare. Minor naturally occurring variants in NA can affect antiviral susceptibility.

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  • Authors+Show Affiliations

    ,

    Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

    , , , , , , , , ,

    Source

    Journal of virology 84:19 2010 Oct pg 9800-9

    MeSH

    Animals
    Antiviral Agents
    Birds
    Catalytic Domain
    Cyclopentanes
    Drug Resistance, Viral
    Enzyme Inhibitors
    Guanidines
    Humans
    Influenza A Virus, H1N1 Subtype
    Influenza A virus
    Influenza in Birds
    Influenza, Human
    Models, Molecular
    Mutation
    Neuraminidase
    Orthomyxoviridae Infections
    Oseltamivir
    Protein Conformation
    Species Specificity
    Swine
    Swine Diseases
    Viral Proteins
    Zanamivir

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20660186

    Citation

    Stoner, Terri D., et al. "Antiviral Susceptibility of Avian and Swine Influenza Virus of the N1 Neuraminidase Subtype." Journal of Virology, vol. 84, no. 19, 2010, pp. 9800-9.
    Stoner TD, Krauss S, DuBois RM, et al. Antiviral susceptibility of avian and swine influenza virus of the N1 neuraminidase subtype. J Virol. 2010;84(19):9800-9.
    Stoner, T. D., Krauss, S., DuBois, R. M., Negovetich, N. J., Stallknecht, D. E., Senne, D. A., ... Webster, R. G. (2010). Antiviral susceptibility of avian and swine influenza virus of the N1 neuraminidase subtype. Journal of Virology, 84(19), pp. 9800-9. doi:10.1128/JVI.00296-10.
    Stoner TD, et al. Antiviral Susceptibility of Avian and Swine Influenza Virus of the N1 Neuraminidase Subtype. J Virol. 2010;84(19):9800-9. PubMed PMID: 20660186.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Antiviral susceptibility of avian and swine influenza virus of the N1 neuraminidase subtype. AU - Stoner,Terri D, AU - Krauss,Scott, AU - DuBois,Rebecca M, AU - Negovetich,Nicholas J, AU - Stallknecht,David E, AU - Senne,Dennis A, AU - Gramer,Marie R, AU - Swafford,Seth, AU - DeLiberto,Tom, AU - Govorkova,Elena A, AU - Webster,Robert G, Y1 - 2010/07/21/ PY - 2010/7/28/entrez PY - 2010/7/28/pubmed PY - 2010/9/30/medline SP - 9800 EP - 9 JF - Journal of virology JO - J. Virol. VL - 84 IS - 19 N2 - Influenza viruses of the N1 neuraminidase (NA) subtype affecting both animals and humans caused the 2009 pandemic. Anti-influenza virus NA inhibitors are crucial early in a pandemic, when specific influenza vaccines are unavailable. Thus, it is urgent to confirm the antiviral susceptibility of the avian viruses, a potential source of a pandemic virus. We evaluated the NA inhibitor susceptibilities of viruses of the N1 subtype isolated from wild waterbirds, swine, and humans. Most avian viruses were highly or moderately susceptible to oseltamivir (50% inhibitory concentration [IC(50)], <5.1 to 50 nM). Of 91 avian isolates, 7 (7.7%) had reduced susceptibility (IC(50), >50 nM) but were sensitive to the NA inhibitors zanamivir and peramivir. Oseltamivir susceptibility ranged more widely among the waterbird viruses (IC(50), 0.5 to 154.43 nM) than among swine and human viruses (IC(50), 0.33 to 2.56 nM). Swine viruses were sensitive to oseltamivir, compared to human seasonal H1N1 isolated before 2007 (mean IC(50), 1.4 nM). Avian viruses from 2007 to 2008 were sensitive to oseltamivir, in contrast to the emergence of resistant H1N1 in humans. Susceptibility remained high to moderate over time among influenza viruses. Sequence analysis of the outliers did not detect molecular markers of drug-resistance (e.g., H275Y NA mutation [N1 numbering]) but revealed mutations outside the NA active site. In particular, V267I, N307D, and V321I residue changes were found, and structural analyses suggest that these mutations distort hydrophobic pockets and affect residues in the NA active site. We determined that natural oseltamivir resistance among swine and wild waterbirds is rare. Minor naturally occurring variants in NA can affect antiviral susceptibility. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/20660186/Antiviral_susceptibility_of_avian_and_swine_influenza_virus_of_the_N1_neuraminidase_subtype_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&amp;pmid=20660186 DB - PRIME DP - Unbound Medicine ER -