TY - JOUR
T1 - 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
AU - Baranovich, Tatiana
AU - Bahl, Justin
AU - Marathe, Bindumadhav M.
AU - Culhane, Marie
AU - Stigger-Rosser, Evelyn
AU - Darnell, Daniel
AU - Kaplan, Bryan S.
AU - Lowe, James F.
AU - Webby, Richard J.
AU - Govorkova, Elena A.
N1 - Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health , under contract numbers HHSN266200700005C and HHSN272201400006C and by ALSAC . The authors thank Jianling Armstrong, Jeri Carol Crumpton, Adam Rubrum, and Kristi Ann Prevost for technical support and Angela J. McArthur for scientific editing the manuscript. The NAIs oseltamivir carboxylate (oseltamivir) and zanamivir were provided by Hoffmann-La Roche, Ltd. (Basel, Switzerland). The NAI peramivir was provided by BioCryst Pharmaceuticals (Birmingham, AL).
Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2015/5
Y1 - 2015/5
N2 - 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.
AB - 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.
KW - Amantadine
KW - Antiviral resistance
KW - Neuraminidase inhibitors
KW - Oseltamivir
KW - Porcine influenza virus
KW - Swine influenza virus
UR - http://www.scopus.com/inward/record.url?scp=84923809006&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923809006&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2015.02.004
DO - 10.1016/j.antiviral.2015.02.004
M3 - Article
C2 - 25701593
AN - SCOPUS:84923809006
VL - 117
SP - 10
EP - 19
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
ER -