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Influenza A viruses of swine circulating in the United States during 2009-2014 are susceptible to neuraminidase inhibitors but show lineage-dependent resistance to adamantanes

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  • Influenza A viruses of swine circulating in the United States during 2009-2014 are susceptible to neuraminidase inhibitors but show lineage-dependent resistance to adamantanes

    Antiviral Res. 2015 Feb 19. pii: S0166-3542(15)00032-7. doi: 10.1016/j.antiviral.2015.02.004. [Epub ahead of print]
    Influenza A viruses of swine circulating in the United States during 2009-2014 are susceptible to neuraminidase inhibitors but show lineage-dependent resistance to adamantanes.

    Baranovich T1, Bahl J2, Marathe BM1, Culhane M3, Stigger-Rosser E1, Darnell D1, Kaplan BS1, Lowe JF4, Webby RJ1, Govorkova EA5.
    Author information

    Abstract

    Antiviral drug susceptibility is one of the evaluation criteria of pandemic potential posed by an influenza virus. Influenza A viruses of swine (IAV-S) can play an important role in generating novel variants, yet limited information is available on the drug resistance profiles of IAV-S circulating in the U.S. Phenotypic analysis of the IAV-S isolated in the U.S. (2009-2011) (n=105) revealed normal inhibition by the neuraminidase (NA) inhibitors (NAIs) oseltamivir, zanamivir, and peramivir. Screening NA sequences from IAV-S collected in the U.S. since 1930 showed 0.03% (1/3396) sequences with clinically relevant H274Y-NA substitution. Phenotypic analysis of IAV-S isolated in the U.S. (2009-2011) confirmed amantadine resistance caused by the S31N-M2 and revealed an intermediate level of resistance caused by the I27T-M2. The majority (96.7%, 589/609) of IAV-S with the I27T-M2 in the influenza database were isolated from pigs in the U.S. The frequency of amantadine-resistant markers among IAV-S in the U.S. was high (71%), and their distribution was M-lineage dependent. All IAV-S of the Eurasian avian M lineage were amantadine-resistant and possessed either a single S31N-M2 substitution (78%, 585/747) or its combination with the V27A-M2 (22%, 162/747). The I27T-M2 substitution accounted for 43% (429/993) of amantadine resistance in classic swine M lineage. Phylogenetic analysis showed that both S31N-M2 and I27T-M2 emerged stochastically but appeared to be fixed in the U.S. IAV-S population. This study defines a drug-susceptibility profile, identifies the frequency of drug-resistant markers, and establishes a phylogenetic approach for continued antiviral-susceptibility monitoring of IAV-S in the U.S.
    Copyright ? 2015. Published by Elsevier B.V.


    KEYWORDS:

    Adamantanes; Amantadine; Antiviral resistance; Neuraminidase inhibitors; Oseltamivir; Peramivir; Porcine influenza virus; Swine influenza virus; Zanamivir

    PMID: 25701593 [PubMed - as supplied by publisher]
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