Full Genome Characterization of Human Influenza A/H3N2 Isolates from Asian Countries Reveals a Rare Amantadine Resistance-Conferring Mutation and Novel PB1-F2 Polymorphisms.
Full Genome Characterization of Human Influenza A/H3N2 Isolates from Asian Countries Reveals a Rare Amantadine Resistance-Conferring Mutation and Novel PB1-F2 Polymorphisms.
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DOI：
10.3389/fmicb.2016.00262
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发表时间：
2016
影响因子：
5.2
通讯作者：
Saito R
中科院分区：
文献类型：
--
作者：
Zaraket H;Kondo H;Hibino A;Yagami R;Odagiri T;Takemae N;Tsunekuni R;Saito T;Japanese Influenza Collaborative Study Group;Myint YY;Kyaw Y;Oo KY;Tin HH;Lin N;Anh NP;Hang Nle K;Mai le Q;Hassan MR;Shobugawa Y;Tang J;Dbaibo G;Saito R
甲型流感病毒的进化速度很快，需要持续监测，以维持疫苗和抗病毒药物的效力。我们对2012-2015年期间在四个亚洲国家（日本、黎巴嫩、缅甸和越南）收集的100株甲型流感/H3 N2分离株进行了下一代测序分析。系统发育分析揭示了几个重配事件，导致多个分支的循环在同一个季节。这在2013年和2013/2014赛季尤为明显。重要的是，我们的数据显示，某些血统似乎更适合，并能够坚持到下一个赛季。大多数A/H3 N2病毒继续携带M2-S31 N突变，从而产生金刚烷胺耐药性。此外，在2014/2015年季节期间在日本获得的三个分离株中检测到M2蛋白中的S31 D突变，其赋予与S31 N突变相似的耐药性水平。没有分离株具有NA-H274 Y突变赋予奥司他韦耐药，但少数分离株被发现含有在催化残基151（D151 A/G/N或V）的NA蛋白的突变。这些变异不会改变对神经氨酸酶抑制剂的敏感性，并且在原始临床标本中未检出，表明它们是在MDCK细胞中传代期间获得的。在PB 1-F2开放阅读框中检测到新的多态性，导致24-34个氨基酸长度的蛋白质截短。因此，这项研究已经证明了监测流感病毒的全基因组以允许检测潜在最适合的谱系的实用性。这增强了我们预测最有可能持续到下一个季节的毒株的能力，并预测疫苗与当年季节性流感季节的潜在匹配或不匹配程度。这将使公共卫生和临床团队能够为任何相关的医疗保健负担做好准备，这取决于该季节的疫苗匹配预测是好还是差。
Influenza A viruses evolve at a high rate requiring continuous monitoring to maintain the efficacy of vaccines and antiviral drugs. We performed next generation sequencing analysis of 100 influenza A/H3N2 isolates collected in four Asian countries (Japan, Lebanon, Myanmar, and Vietnam) during 2012–2015. Phylogenetic analysis revealed several reassortment events leading to the circulation of multiple clades within the same season. This was particularly evident during the 2013 and 2013/2014 seasons. Importantly, our data showed that certain lineages appeared to be fitter and were able to persist into the following season. The majority of A/H3N2 viruses continued to harbor the M2-S31N mutation conferring amantadine-resistance. In addition, an S31D mutation in the M2-protein, conferring a similar level of resistance as the S31N mutation, was detected in three isolates obtained in Japan during the 2014/2015 season. None of the isolates possessed the NA-H274Y mutation conferring oseltamivir-resistance, though a few isolates were found to contain mutations at the catalytic residue 151 (D151A/G/N or V) of the NA protein. These variations did not alter the susceptibility to neuraminidase inhibitors and were not detected in the original clinical specimens, suggesting that they had been acquired during their passage in MDCK cells. Novel polymorphisms were detected in the PB1-F2 open-reading frame resulting in truncations in the protein of 24–34 aminoacids in length. Thus, this study has demonstrated the utility of monitoring the full genome of influenza viruses to allow the detection of the potentially fittest lineages. This enhances our ability to predict the strain(s) most likely to persist into the following seasons and predict the potential degree of vaccine match or mismatch with the seasonal influenza season for that year. This will enable the public health and clinical teams to prepare for any related healthcare burden, depending on whether the vaccine match is predicted to be good or poor for that season.