贵州省人类肠道病毒的遗传多样性及变异变迁规律研究

Human enteroviruses (HEV) are the most common causative agents infecting human, causing many harmful diseases，such as acute flaccid paralysis (AFP)， myocarditis，hand,foot and mouth disease (HFMD)，herpangina (HA)，and aseptic meningitis. HEV may also lead to severe outcomes and even death. HEV related diseases pose a serious worldwide threat to public health. Guizhou is one of the regions with high incidence of HEV related diseases. In the past 20 years，the rate of separation of the non-polio enterovirus (NPEV) in AFP stool samples has been more than 10%. In addition，cases of HFMD have long been in the top of class c infectious diseases in Guizhou province between 2009 to 2017，but the dynamic change in variation and genetic diversity of HEV were not clearly understood. In this project，based on the discovery of 47 enterovirus serotypes in the previous study，we are planning to reveal the genetic diversity and variation of HEV strains from the AFP and HFMD patients in Guizhou province，and to reveal the molecular evolution among the HEV isolated from Guizhou and other domestic and overseas by whole genome sequences comparation and bioinformatics methods，and therefore，this may be used to establish the pedigree of enterovirus serotypes，to accumulate the baseline data of molecular characteristics of HEV isolated，and also it is very useful for identification of the transmission chains of HEV in Guizhou. Based on the knowledge of genetic evolution of HEV of human-to-human transmission，their genomic features and the pattern of circulation could be well understood，this project will contribute important scientific information to the prevention and control of related diseases and the establishment of precaution mechanism.

人类肠道病毒（HEV）可引起急性弛缓性麻痹（AFP）、心肌炎、手足口病（HFMD）和无菌性脑炎等多种疾病，人群普遍易感且可致死亡，已成为非常严重的公共卫生问题。贵州省是HEV相关疾病的高发地区之一，近20年来AFP病例监测中非脊灰肠道病毒（NPEV）的分离率平均在10%以上，另外在2009-2017年间HFMD的病例长期位于贵州省丙类传染病中的首位，但目前贵州地区HEV遗传多样性及变异变迁规律并不完全清楚。本项目拟在前期研究已发现47种HEV血清型别的基础上，进一步对覆盖全省的AFP与HFMD监测系统中分离到的毒株进行分子鉴定，结合基因组测序和生物信息学分析，探索HEV区域性流行谱和遗传变异规律，阐明贵州地区HEV与国内外同型病毒的分子差别和进化关系，累积HEV的分子特征本底资料，为查明今后可能的HEV流行株的来源提供依据，为HEV所致相关疾病的防控和建立预测预警机制奠定基础。

人类肠道病毒（Human Enteroviruses, HEV）可引起急性弛缓性麻痹（Acute Flaccid Paralysis,AFP）、无菌性脑炎、心肌炎、手足口病（Hand, foot and mouth disease, HFMD）等疾病，严重可致重症或死亡。基于覆盖全省的AFP与HFMD监测系统，为探讨本地区肠道病毒病原谱及遗传变异规律，开展如下工作：1.1997-2021年共监测AFP病例5770例，获得非脊灰肠道病毒（Non-polio Enteroviruses，NPEV）660株，从中鉴定出52种肠道病毒血清型，涉及肠道病毒A组9种、B组36种和C组7种，其中还包括柯萨奇病毒A7；2.2018-2021年，从75份重症HFMD病例标本中，成功分离得到32株病毒株，型别主要包括肠道病毒A组7种、B组3种，其中2例患者为混合感染；3.肠道病毒A组与B组血清型至今还在本地区传播流行，而肠道病毒B组至从2004年以后就未发现；4.在AFP与HFMD病例中，存在同一型别肠道病毒感染，其病毒基因序列高度同源，但有个别病毒株，其不同的血清亚型在不同病例中传播；5. 肠道病毒感染的病例全省均有分布，好发于男性，以儿童为主，春夏季节为高发季节；6.AFP病例监测发现，本地区脊灰疫苗的接种率较高，大于5剂次接种普遍存在，但接种疫苗或（和）剂次的增加与NPEV感染没有相关性；7.基于基于MCDA-LFB技术，建立手足口病重要病原CV-A16与EV-A71的快速检测体系及应用。基于以上结果，得如下结论：1. 初步阐明贵州地区肠道病毒病原谱，构建出本地区肠道病毒分子流行病学基线数据；2. 首次在国内AFP病例鉴定得到柯萨奇病毒A7病毒株，系统进化分析该病毒基因组可能存在重组变异；3. 脊灰疫苗接种与NPEV感染没有相关性；4.建立了HFMD重要病原快速检测方法。该项目有助于为本地区肠道病毒病防控策略、预警机制及快速检测提供科学依据。

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