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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

tetano

Editor, Senior Moderator
Antiviral Res. 2015 Feb 19. pii: S0166-3542(15)00032-7. doi: 10.1016/j.antiviral.2015.02.004. [Epub ahead of print]
[h=1]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.[/h] Baranovich T[SUP]1[/SUP], Bahl J[SUP]2[/SUP], Marathe BM[SUP]1[/SUP], Culhane M[SUP]3[/SUP], Stigger-Rosser E[SUP]1[/SUP], Darnell D[SUP]1[/SUP], Kaplan BS[SUP]1[/SUP], Lowe JF[SUP]4[/SUP], Webby RJ[SUP]1[/SUP], Govorkova EA[SUP]5[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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.


[h=4]KEYWORDS:[/h] 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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