Infection and Drug Resistance (Oct 2018)
Antiviral resistance markers in influenza virus sequences in Mexico, 2000–2017
Abstract
William Toledo-Rueda,1,2 Nora H Rosas-Murrieta,3 José E Muñoz-Medina,4 César R González-Bonilla,4 Julio Reyes-Leyva,1 Gerardo Santos-López1 1Laboratory of Molecular Biology and Virology, Eastern Biomedical Research Center, Mexican Institute of Social Security, Metepec, Puebla, Mexico; 2Postgraduate in Chemical Sciences, Autonomous University of Puebla, Puebla, Mexico; 3Laboratory of Biochemistry and Molecular Biology, Chemistry Center, Institute of Science, Autonomous University of Puebla, Puebla, Mexico; 4Division of Laboratories for Surveillance and Epidemiological Research, Coordination of Epidemiological Surveillance, Mexican Institute of Social Security, Mexico City, Mexico. Background: Influenza causes high rates of morbidity and mortality. Genetic variability of influenza viruses generates resistance to antivirals, which are of two types, since they act on two different viral targets: adamantanes, which block the M2 ion channel, and the neuraminidase (NA) inhibitors. Methods: In Mexico, the available studies on the antiviral resistance of circulating influenza strains are scarce, so this work undertook an analysis of the Mexican sequences reported in public gene banks to perform a systematic analysis of the antiviral resistance markers on both M2 and NA. In all, 284 M2 sequences and 423 NA sequences were retrieved from three genetic databases (sequences from 2000 to 2017 were considered). Results: The resistance markers to M2 blockers were present in 100% of H1N1 pdm2009, 83.6% of H3N2, and 5.8% of seasonal H1N1 sequences. Two resistance markers conferring resistance to NA inhibitors were present in seasonal H1N1 sequences, H275Y (50.0%) and N70S (33.3%). None of these viruses had both resistance markers, which are associated with oseltamivir resistance. The more frequent resistance marker in H1N1 pdm2009 NA sequences was H275Y, present in 3.6%, while S247N was present in 0.30%. Only one of the resistance-associated markers (Q136K) in NA (1.5%) was present in the analyzed H3N2 sequences, while sequences of influenza B virus did not present resistance markers to NA inhibitors. Some influenza A H1N1 pdm2009 sequences (1.8%) presented resistance markers to both M2 and NA. Conclusion: Based on the present analysis, 7.1% of the all serotypes of influenza virus A sequences analyzed in Mexico from 2000 to 2017 have mutations conferring resistance to NA inhibitors. Because of this, and the limited availability of influenza drugs, it is necessary to increase the epidemiological surveillance, including molecular analysis, which will provide data such as the presence of changes associated with antiviral resistance. Keywords: influenza A virus, drug resistance, M2 blockers, neuraminidase inhibitors, oseltamivir, zanamivir
