上海季節性H3N2病毒的全基因組特徵揭示了溫度敏感株是由PA上I668V突變賦予的！

近日，上海交通大學瑞金醫學院的研究人員在Emerging Microbes & Infections雜誌上發表了如下圖的研究。

季節性H3N2流感病毒被認為是主要的流行病毒，在溫帶氣候地區表現出複雜的季節性類型。為調查季節性流感的病毒進化和變異，研究者收集了上海2016-2017年62例H3N2感染病例的標本，並做了一個基因組分析。

甲型流感病毒所有八個部分的進化分析顯示，有兩種流行性感冒病毒在2016-2017年的冬季和2017年夏季流行。研究者還測量了這兩種流行株在不同溫度（33, 35, 37和39 °C）下的複製，並分析了溫度敏感性的兩種流行株的突變和病毒複製間的關聯。複製動力學分析顯示2016-2017年冬季流行株的複製在39 °C明顯受到限制，與2017年夏季流行株相比。一個聚合酶活性實驗和突變分析證明了2016-2017年冬季流行株PA （acidic polymerase）基因上I668V的突變抑制了高溫時試管內實驗的聚合酶活性。

圖1 對流行於2016年11月-2017年9月HA和NA片段的進化分析

總之，這些數據表明2016-2017年冬季流行株的PA亞單位可以賦予病毒溫度敏感性，並減弱病毒的複製和聚合酶活性。同時，2017年夏季流行株在高溫時能保持毒力。這些發現強調了某些突變在病毒複製及隨後季節里的持久性上的重要性。

Abstract

Seasonal H3N2 influenza viruses are recognized as major epidemic viruses, exhibiting complex seasonal patterns in regions with temperate climates. To investigate the influence of viral evolution and mutations on the seasonality of influenza, we performed a genome-wide analysis of samples collected from 62 influenza A/H3N2-infected patients in Shanghai during 2016–2017. Phylogenetic analysis of all eight segments of the influenza A virus revealed that there were two epidemic influenza virus strains circulating in the 2016–2017 winter season (2016–2017win) and2017 summer season (2017sum). Replication of the two epidemic viral strains at different temperatures (33, 35, 37, and 39 °C) was measured, and the correlation of the mutations in the two epidemic viral strains with temperature sensitivity and viral replication was analyzed. Analysis of the replication kinetics showed that replication of the 2016–2017win strains was significantly restricted at 39 °C compared with that of the 2017sum strains. A polymeraseactivity assay and mutational analysis demonstrated that the PA I668V mutation of the 2016–2017win viruses suppressed polymerase activity in vitro at high temperatures. Taken together, these data suggest that the I668V mutation in the PA subunit of the 2016–2017win strains may confer temperature sensitivity and attenuate viral replication and polymerase activity; meanwhile, the 2017sum strains maintained virulence at high temperatures. Thesefindings highlight the importance of certain mutations in viral adaptation and persistence in subsequent seasons.

DOI 10.1038/s41426-018-0172-4

本期編輯：烏龜

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