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

Tatiana Baranovich, Justin Bahl, Bindumadhav M. Marathe, Marie Culhane, Evelyn Stigger-Rosser, Daniel Darnell, Bryan S. Kaplan, James F. Lowe, Richard J. Webby, Elena A. Govorkova

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13 Scopus citations

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. (1930-2014) 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.

Original languageEnglish (US)
Pages (from-to)10-19
Number of pages10
JournalAntiviral Research
Volume117
DOIs
StatePublished - May 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.

Keywords

  • Amantadine
  • Antiviral resistance
  • Neuraminidase inhibitors
  • Oseltamivir
  • Porcine influenza virus
  • Swine influenza virus

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