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Antiviral Agents

Antiviral Susceptibility of Variant Influenza A(H3N2)v Viruses Isolated in the United States from 2011 to 2013

K. Sleeman, V. P. Mishin, Z. Guo, R. J. Garten, A. Balish, A. M. Fry, J. Villanueva, J. Stevens, L. V. Gubareva
K. Sleeman
aVirology, Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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V. P. Mishin
aVirology, Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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Z. Guo
aVirology, Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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R. J. Garten
aVirology, Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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A. Balish
aVirology, Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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A. M. Fry
bEpidemiology and Prevention Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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J. Villanueva
aVirology, Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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J. Stevens
aVirology, Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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L. V. Gubareva
aVirology, Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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DOI: 10.1128/AAC.02556-13
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ABSTRACT

Since 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have become a public health concern in the United States. The A(H3N2)v viruses share the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but do not contain any known molecular markers associated with resistance to neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI) assay, the susceptibilities of recovered A(H3N2)v viruses (n = 168) to FDA-approved (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs were assessed. All A(H3N2)v viruses tested, with the exception of a single virus strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold) and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins, S247P was shown to be responsible for the observed altered NAI susceptibility, in addition to an approximately 60% reduction in NA enzymatic activity. The S247P substitution has not been previously reported as a molecular marker of reduced susceptibility to the NAIs. Using cell culture assays, the investigational antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the replication of A(H3N2)v viruses, including the virus with the S247P substitution in the NA. This report demonstrates the importance of continuous monitoring of susceptibility of zoonotic influenza viruses to available and investigational antiviral drugs.

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Antiviral Susceptibility of Variant Influenza A(H3N2)v Viruses Isolated in the United States from 2011 to 2013
K. Sleeman, V. P. Mishin, Z. Guo, R. J. Garten, A. Balish, A. M. Fry, J. Villanueva, J. Stevens, L. V. Gubareva
Antimicrobial Agents and Chemotherapy Mar 2014, 58 (4) 2045-2051; DOI: 10.1128/AAC.02556-13

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Antiviral Susceptibility of Variant Influenza A(H3N2)v Viruses Isolated in the United States from 2011 to 2013
K. Sleeman, V. P. Mishin, Z. Guo, R. J. Garten, A. Balish, A. M. Fry, J. Villanueva, J. Stevens, L. V. Gubareva
Antimicrobial Agents and Chemotherapy Mar 2014, 58 (4) 2045-2051; DOI: 10.1128/AAC.02556-13
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