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

Memórias do Instituto Oswaldo Cruz

Thiago Moreno Lopes E Souza¹  Natalia Fintelman-rodrigues¹  Paola Cristina Resende¹  Milene Mesquita¹  Tatiana Schaffer Gregianini¹  Fernando A Bozza¹  Ana Carla Pecego¹  Sandra Bianchini Fernandes¹  Ana Luisa Furtado Cury¹  Irina Nastassja Riediger¹  Marilda M Siqueira¹ 

关键词: influenza A(H1N1)pdm09;    oseltamivir;    antiviral;    resistance;    H275Y;    permissive mutation;   

DOI  :  10.1590/0074-02760140330

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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