Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Poultry, Vietnam, 2009–2011 - Vol. 19 No. 12 - December 2013 - Emerging Infectious Disease journal - CDC
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Volume 19, Number 12—December 2013
Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Poultry, Vietnam, 2009–2011
AbstractWe assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated from poultry in Vietnam during 2009–2011. Of 25 clade 1.1 viruses, all possessed a marker of resistance to M2 blockers amantadine and rimantadine; 24 were inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses contained a I223T mutation and showed 7-fold reduced inhibition by oseltamivir. One of 70 clade 126.96.36.199 viruses had the H275Y marker of oseltamivir resistance and exhibited highly reduced inhibition by oseltamivir and peramivir; antiviral agents DAS181 and favipiravir inhibited H275Y mutant virus replication in MDCK-SIAT1 cells. Replicative fitness of the H275Y mutant virus was comparable to that of wildtype virus. These findings highlight the role of drug susceptibility monitoring of H5N1 subtype viruses circulating among birds to inform antiviral stockpiling decisions for pandemic preparedness.
Genetic and antigenic divergence of HPAI (H5N1) viruses among poultry challenges development of effective vaccines for poultry and to pandemic preparedness and development of antiviral drugs for humans. Assessment of drug susceptibility has become an integral part of subtype H5N1 virus surveillance. To assist laboratories worldwide in their surveillance and pandemic preparedness efforts, the Influenza Division of the Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA, along with other partners, developed the H5N1 Genetic Changes Inventory that includes established and potential markers of drug resistance (5). Resistance to matrix 2 (M2) protein blockers amantadine and rimantadine, caused by mutations in the M2 protein, is detected commonly in clade 1.1 (S31N) and clade 2.1.3 (V27A) H5N1 virus subtypes and sporadically in other groups (6,7). Oseltamivir, an orally administered neuraminidase (NA) inhibitor, is the most prescribed medication for the treatment of persons with influenza virus infections. Emergence of resistance to NA inhibitors among H5N1 virus subtypes, especially oseltamivir resistance among H5N1 subtypes caused by the H275Y mutation, is a constant threat (8). Assessment of susceptibility to NA inhibitors is hampered by several factors: insufficient knowledge of molecular markers of resistance, lack of harmonized approaches for testing and data analysis and, most critically, lack of established laboratory correlates of clinically relevant resistance. Taking into account these and other limitations, the current method for monitoring susceptibility to NA inhibitors is a critical element needed to evaluate pandemic risk.
In this study, we assessed drug susceptibility profiles of HPAI A(H5N1) viruses isolated from poultry specimens collected in Vietnam during 2009–2011. The antiviral drugs tested included FDA-approved medications and investigational antiviral agents. We report the detection of an oseltamivir-resistant virus with H275Y mutation from the expanding clade 188.8.131.52.
Dr Ha T. Nguyen is a Battelle research scientist on the Molecular Epidemiology Team of the Influenza Division, Centers for Disease Control and Prevention, in Atlanta, Georgia. Her research interests include influenza viruses and mechanisms of resistance to antiviral agents.
We thank our collaborators in the National Center for Veterinary Diagnostics, Hanoi, Vietnam, for their valuable contributions to this study. We also thank Ronald B. Moss and Yousuke Furuta for kindly providing investigational anti-influenza drugs DAS181 and favipiravir, respectively, and Anton Chesnokov for his excellent technical assistance.
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Suggested citation for this article: Nguyen HT, Nguyen T, Mishin VP, Sleeman K, Balish A, Jones J, et al. Antiviral susceptibility of highly pathogenic avian influenza A(H5N1) viruses isolated from poultry, Vietnam, 2009–2011. Emerg Infect Dis. 2013 Dec [date cited]. http://dx.doi.org/10.3201/eid1912.130705