摘要
目的应用生物信息学数据库和工具，对现有的H5亚型甲型流感病毒全球分离株的H5A1抗原序列进化规律进行研究。方法下载NCBI Genbank和美国洛斯阿莫斯国家实验室流感病毒数据库中全部的甲型流感病毒H5A1序列，采用快速极大似然法绘制进化树，并用SRDT模型估计各分枝的进化速度与出现时间。结果H5A1序列的进化树可被分为两个各自独立进化的世系：美洲世系和欧／亚世系，它们在地域分布、序列位点等方面区别明显，且可被进一步细分为几大进化枝，野生禽类分枝和家禽株系分枝的进化速度存在明显差异，所有的人及其他哺乳动物感染株系则均来自于欧／亚世系的亚洲禽／人分枝。结论H5A1序列在野生禽类中已达到相对稳定的状态，其自然变异速度为（1．990-2．535）×10^-3／位点／年，而家禽中的高毒力变异株进化速度明显加快。目前威胁人类的主要是1996年之后出现的亚洲变异株，且进化树结构提示该株系出现过多次禽／人跨宿主传播事件，值得对其位点特征进行深入研究。
Purpose H5 influenza virus remains a potential threaten to human health. Analysis of the accumulated strain data provides a new way to understand its evolution tendency. With the help of latest developed hioinformatics tools, all available Influenza H5A1 strains were explored to deeply understand their evolution tendency. Methods All H5A1 sequence in NCBI genhank and influenza se- quence database were downloaded and aligned, then fast maximizing likelihood method was applied to construct phylogenetic tree, and SRDT model was used to estimate evolution rate and ancestral date for tree branches. Results Tree topology indicated that H5A1 strains evolved along two independent lineages： American lineage and European/Asian lineage. These two lineages, with distinctive difference over place and site variation, could be further split into several branches. Evolution speed for avi- an branches and poultry branches were quite different. All human infected strains were belonging to Asian poultry/human lineage. Conclusions While much higher in poultry, H5A1 strains have reached a stable status in different sublineages of wide avian, the rate among wild avian was （1. 990 - 2. 535） × 10^-3 nucleotide substitution per site per year. The main potential threat to human is Asian high virulence variation strains. Since repeated avian-human interspecies transmission events were observed for these mutations, further investigation is needed to elucidate variation patterns of nucleotide sites.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2007年第1期17-23,共7页
Fudan University Journal of Medical Sciences
基金
国家自然科学基金项目(30400370)
关键词
甲型流感病毒
血凝素
H5亚型
进化树
进化速度
influenza A virus
hemagglutinin
H5 subtype
phylogenetic tree
evolution rate
