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首页> 外文期刊>Memórias do Instituto Oswaldo Cruz >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
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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

机译：在巴西发现的耐Oseltamivir的甲型H1N1流感pdm2009菌株具有允许的突变，可补偿因抗病毒耐药性导致的适应性丧失

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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.
机译：2009年的甲型流感大流行爆发导致系统使用神经氨酸酶（NA）抑制剂奥司他韦（OST）。因此，在大流行之后的几年中出现了带有突变H275Y的OST抗性菌株，流行率为1-2％。当前，在社区环境中未治疗的个体中发现了抗OST菌株。为了在社区环境中传播，H275Y突变体必须包含其他突变，统称为许可突变。我们显示在巴西社区环境中发现的耐OST的A（H1N1）pdm09病毒在NA中的允许突变。 2013年的NA在系统发育上与2012年不同，这表明积极选择具有更好适应性的NA的趋势。在巴西也发现了一些先前预测的允许突变，例如在不同国家发现的V241I和N369K。重要的是，在巴西发现了D344N的变化，该变化也预示着可以弥补H275Y突变造成的适应性丧失，但在2013年的其他国家中却没有。我们的结果进一步证明了具有补偿性突变的抗OST抗性A（H1N1）pdm09菌株可能样品以独立的方式产生，并在巴西不同州和不同国家/地区进行了样品鉴定。这些病毒株的系统性循环将来可能会危害第一线抗流感药物的使用。

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