Detection of Resistance Mutations to Antivirals Oseltamivir and Zanamivir in Avian Influenza A Viruses Isolated from Wild Birds
Open Access
- 6 January 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (1), e16028
- https://doi.org/10.1371/journal.pone.0016028
Abstract
The neuraminidase (NA) inhibitors oseltamivir and zanamivir are the first-line of defense against potentially fatal variants of influenza A pandemic strains. However, if resistant virus strains start to arise easily or at a high frequency, a new anti-influenza strategy will be necessary. This study aimed to investigate if and to what extent NA inhibitor–resistant mutants exist in the wild population of influenza A viruses that inhabit wild birds. NA sequences of all NA subtypes available from 5490 avian, 379 swine and 122 environmental isolates were extracted from NCBI databases. In addition, a dataset containing 230 virus isolates from mallard collected at Ottenby Bird Observatory (Öland, Sweden) was analyzed. Isolated NA RNA fragments from Ottenby were transformed to cDNA by RT-PCR, which was followed by sequencing. The analysis of genotypic profiles for NAs from both data sets in regard to antiviral resistance mutations was performed using bioinformatics tools. All 6221 sequences were scanned for oseltamivir- (I117V, E119V, D198N, I222V, H274Y, R292K, N294S and I314V) and zanamivir-related mutations (V116A, R118K, E119G/A/D, Q136K, D151E, R152K, R224K, E276D, R292K and R371K). Of the sequences from the avian NCBI dataset, 132 (2.4%) carried at least one, or in two cases even two and three, NA inhibitor resistance mutations. Swine and environmental isolates from the same data set had 18 (4.75%) and one (0.82%) mutant, respectively, with at least one mutation. The Ottenby sequences carried at least one mutation in 15 cases (6.52%). Therefore, resistant strains were more frequently found in Ottenby samples than in NCBI data sets. However, it is still uncertain if these mutations are the result of natural variations in the viruses or if they are induced by the selective pressure of xenobiotics (e.g., oseltamivir, zanamivir).Keywords
This publication has 64 references indexed in Scilit:
- Influenza Virus Evolution, Host Adaptation, and Pandemic FormationCell Host & Microbe, 2010
- Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir ResistanceScience, 2010
- Emergence of H5N1 avian influenza viruses with reduced sensitivity to neuraminidase inhibitors and novel reassortants in Lao People's Democratic RepublicJournal of General Virology, 2010
- In Vitro Generation of Neuraminidase Inhibitor Resistance in A(H5N1) Influenza VirusesAntimicrobial Agents and Chemotherapy, 2009
- Influenza Virus Resistance to Antiviral Agents: A Plea for Rational UseClinical Infectious Diseases, 2009
- Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human SialidasesAntimicrobial Agents and Chemotherapy, 2008
- Low Penetration of Oseltamivir and Its Carboxylate into Cerebrospinal Fluid in Healthy Japanese and Caucasian VolunteersAntimicrobial Agents and Chemotherapy, 2008
- Strategies for mitigating an influenza pandemicNature, 2006
- Mitigation strategies for pandemic influenza in the United StatesProceedings of the National Academy of Sciences of the United States of America, 2006
- Universal primer set for the full-length amplification of all influenza A virusesArchiv für die gesamte Virusforschung, 2001