National Influenza Centre for Northern Greece, Microbiology Department, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
J Med Virol. 2015 Jan;87(1):57-67. doi: 10.1002/jmv.23990. Epub 2014 Jun 5.
Since its appearance, influenza A(H1N1)pdm09 caused considerable morbidity and mortality in Northern Greece. Genetic analysis of post-pandemic circulating strains scoped to investigate any correlation between genetic variations that emerged during viral evolution and severity of infection. Pharyngeal swabs/aspirates (n = 1,870) were examined with real-time reverse transcription-polymerase chain reaction. Hemagglutinin sequences were analyzed on 110 strains (37 fatal/73 non-fatal cases), followed by statistical and phylogenetic analysis. Influenza A(H1N1)pdm09 was detected in 848 samples. Coexistence of clusters 3, 4, 5, 6, and 7 indicated co-circulation of lineages in Northern Greece. Genetic analysis showed that HA sequences had 96-99% sequence similarity with the vaccine strain and that there was no association between any co-circulating lineage and severity. Several viruses accumulated variations in HA antigenic sites. D222G was significantly associated with fatal infections, supporting its association with increased viral pathogenesis. On the other hand, four variations were associated with milder disease outcomes. Certain signature amino acid changes persisted during and/or after the pandemic, indicating their offer of selective advantages to the virus. Negative selection was observed in 70% of pandemic variations as they probably did not contribute to the virus fitness. It is of interest that persistent variations were highly identified in the vicinity of antigenic or receptor-binding sites. Of those, K171R was associated only with fatal infections. Also of interest, only strains that were isolated from fatal infections had variations that altered both their acid-base and polarity properties. Genetic changes that may alter the antigenicity, pathogenicity and transmissibility of circulating virus variants need to be determined and closely monitored.
自出现以来，甲型 H1N1pdm09 在希腊北部造成了相当大的发病率和死亡率。对大流行后循环株的遗传分析旨在研究病毒进化过程中出现的遗传变异与感染严重程度之间的任何相关性。使用实时逆转录聚合酶链反应检查咽拭子/抽吸物（n=1870）。对 110 株（37 例致死/73 例非致死病例）进行血凝素序列分析，随后进行统计和系统发育分析。在 848 个样本中检测到甲型 H1N1pdm09。簇 3、4、5、6 和 7 的共存表明在希腊北部存在谱系的共同循环。遗传分析表明，HA 序列与疫苗株的序列相似度为 96-99%，并且没有任何共同循环谱系与严重程度之间存在关联。一些病毒在 HA 抗原位点积累了变异。D222G 与致死性感染显著相关，支持其与增加的病毒发病机制相关。另一方面，有四个变异与较轻的疾病结果相关。在大流行期间和/或之后，某些特征性氨基酸变化持续存在，表明它们为病毒提供了选择优势。在 70%的大流行变异中观察到负选择，因为它们可能不会对病毒适应性做出贡献。有趣的是，在抗原或受体结合位点附近高度鉴定了持续性变异。其中，K171R 仅与致死性感染相关。同样有趣的是，只有从致死性感染中分离出的菌株才具有改变其酸碱和极性特性的变异。需要确定并密切监测可能改变循环病毒变异体抗原性、致病性和传染性的遗传变化。
