2010⁃2019年北京地区腹泻患儿中人腺病毒41型Fiber基因分子特征和进化分析  

Genetic Variation and Molecular Evolution of the Fiber Gene of Human Adenovirus Serotype 41 Strains in Children Suffering from Diarrhea During 2010–2019 in Beijing,China

作　　者：刘立颖[1] 钱渊[1] 贾立平[1] 董慧谨 朱汝南[1] LIU Liying;QIAN Yuan;JIA Liping;DONG Huijin;ZHU Runan(Laboratory of Virology,Beijing Key Laboratory of Etiology of Viral Diseases in Children,Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所病毒研究室,儿童病毒病病原学北京市重点实验室,北京100020

出　　处：《病毒学报》2021年第5期1102-1111,共10页Chinese Journal of Virology

基　　金：国家自然科学基金青年基金(项目号:81401705),题目:外壳蛋白penton和Fiber在腺病毒31型嗜肠道感染中的作用及机制研究;首都儿科研究所所级基金(项目号:FX-2018-02),题目:腺病毒31型外壳蛋白Fiber抗原表位的研究。

摘　　要：人腺病毒41型(Human adenovirus 41,HAdV-41)是引起儿童腹泻的重要病原之一。为了解北京地区腹泻儿童中HAdV-41 Fiber基因的分子变异和遗传进化特征,选取2010-2019年首都儿科研究所附属儿童医院门诊腹泻患儿HAdV-41阳性的粪便标本,扩增Fiber全基因,使用多种生物信息学软件进行系统发生、遗传进化、种群演变和选择压力等分析。结果显示HAdV-41本地毒株存在1644碱基(547氨基酸)和1689碱基(562氨基酸)两种长度的Fiber基因,截短的15个氨基酸位于Fiber蛋白纤维轴区。Mann-Whitney U秩和检验提示检测到感染短Fiber基因的HAdV-41的患儿年龄更小(P=0.036)。同源性分析结果显示Fiber基因的核苷酸和氨基酸序列同源性均大于97%,主要分为四个进化分支(Ⅰ、Ⅱ、Ⅲ和Ⅳ),其中Ⅰ和Ⅲ是主要的流行分支,分支Ⅰ主要在国内流行,而分支Ⅲ全球均有流行。HAdV-41共祖起源可追溯到1856年,平均进化速率每年为6.81×10^(-5)碱基替换/位点,10年间理论有效种群一直比较平稳呈缓慢下降趋势。压力选择分析表明,一个正向和三个负向选择位点均位于Fiber蛋白的纤维轴区。上述结果表明2010-2019年间不同进化分支的HAdV-41在北京地区流行,进化速率稳定。Fiber蛋白轴区存在两种不同类型的氨基酸缺失。Human adenovirus 41(HAdV-41)is one of the common pathogens causing viral diarrhea in children.HAdV-41-positive fecal samples were selected to investigate the genetic variation and molecular evolution of the fiber gene of HAdV-41 strains circulating among children suffering from diarrhea during 2010–2019 in Beijing,China.The fiber genes were amplified by the polymerase chain reaction and were analyzed for gene phylogeny,genetic evolution,population evolution and selection pressure using bioinformatics software.The results showed that two lengths of 1644 base pairs(547 amino acids)and 1689 base pairs(562 amino acids)of the fiber genes were found and two types of deletion with 15 amino acids were located in the shaft region of the fiber protein.Children infected with HAdV-41 with a truncated fiber gene were younger(P=0.036).Sequencing showed that the nucleotide and amino-acid homologies among fiber genes were>97%,respectively,which were divided mainly into four evolutionary branches(Ⅰ,Ⅱ,ⅢandⅣ).ⅠandⅢwere two major branches,in whichⅠcirculated mainly in China,whereasⅢwas prevalent worldwide.The time to the most recent common ancestor of HAdV-41 could be traced back to 1856.The mean evolutionary rate of HAdV-41 was 6.81×10^(-5)base substitutions/sites/year.During the last decade,the estimated effective population size of HAdV-41 had been relatively stable and decreased slightly.Analyses of selective pressure showed one positive selection site and three negative selection sites were all located in the shaft region of the fiber protein.In conclusion,HAdV-41 strains in different evolutionary branches have been circulating in Beijing during 2010 to 2019 and evolved at a stable rate.There were two distinct types of deletions in the shaft region of fiber proteins.

关 键 词：人腺病毒41型(HAdV-41) 纤维蛋白 腹泻 分子进化 

分 类 号：R373.25[医药卫生—病原生物学]