Oseltamivir-resistant influenza A(H1N1)pdm2009 strains found in Brazil are endowed with permissive mutations, which compensate the loss of fitness imposed by antiviral resistance|
Lopes e Souza, Thiago Moreno; Fintelman-Rodrigues, Natalia; Resende, Paola Cristina; Mesquita, Milene; Gregianini, Tatiana Schaffer; Bozza, Fernando A.; Pecego, Ana Carla; Fernandes, Sandra Bianchini; Cury, Ana Luisa Furtado; Riediger, Irina Nastassja & Siqueira, Marilda M.
The 2009 pandemic influenza A virus outbreak led to the systematic use of the neuraminidase (NA) inhibitor
oseltamivir (OST). Consequently, OST-resistant strains, carrying the mutation H275Y, emerged in the years after the
pandemics, with a prevalence of 1-2%. Currently, OST-resistant strains have been found in community settings, in untreated
individuals. To spread in community settings, H275Y mutants must contain additional mutations, collectively
called permissive mutations. We display the permissive mutations in NA of OST-resistant A(H1N1)pdm09 virus found
in Brazilian community settings. The NAs from 2013 are phylogenetically distinct from those of 2012, indicating a tendency
of positive selection of NAs with better fitness. Some previously predicted permissive mutations, such as V241I
and N369K, found in different countries, were also detected in Brazil. Importantly, the change D344N, also predicted
to compensate loss of fitness imposed by H275Y mutation, was found in Brazil, but not in other countries in 2013. Our
results reinforce the notion that OST-resistant A(H1N1)pdm09 strains with compensatory mutations may arise in an
independent fashion, with samples being identified in different states of Brazil and in different countries. Systematic
circulation of these viral strains may jeopardise the use of the first line of anti-influenza drugs in the future.
influenza A(H1N1)pdm09; oseltamivir; antiviral; resistance; H275Y; permissive mutation