急性呼吸道感染病例中人冠状病毒229E感染情况及病毒基因特征分析  

The Prevalence and Gene Characteristics Analysis of Human Coronavirus 229E Among Acute Respiratory Infection Cases

作　　者：李丰辰 蒋豪然 夏百成 马洪滨 朱汝南[3] 许晶[4] 黄艳智[5] 郜振国[6] 胡孔新[7] 李岩[8] 向星宇[9] 吴巨龙[10] 许红梅[11] 张凤 王文慧 张燕[1] 崔爱利[1] LI Fengchen;JIANG Haoran;XIA Baicheng;MA Hongbin;ZHU Runan;XU Jing;HUANGYanzhi;GAO Zhenguo;HU Kongxin;LI Yan;XIANG Xingyu;WU Julong;XU Hongmei;ZHANG Feng;WANG Wenhui;ZHANG Yan;CUI Aili(National Institute for Viral Disease Control and Prevention,Chinese Centers for Disease Control and Prevention,National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID),NHC Key Laboratory of Medical Virology and Viral Diseases,Beijing 102206,China;The Fifth Medical Center of the PLA General Hospital,Beijing 100039,China;Capital Institute of Pediatrics,Beijing 100020,China;Shaanxi Provincial Centre for Disease Control and Prevention,Xi’an 710054,China;Children's Hospital of Changchun,Changchun 130051,China;Xinjiang Center for Disease Control and Prevention,Urumqi 830002,China;Institute of Health Inspection and Quarantine,Chinese Academy of Inspection and Quarantine,Beijing 100123,China;Hebei Provincial Center for Disease Control and Prevention,Shijiazhuang 050021,China;Hunan Provincial Center for Disease Control and Prevention,Changsha 410005,China;Shandong Provincial Center for Disease Control and Prevention,Jinan 250014,China;Children's Hospital of Chongqing Medical University,Chongqing 400014,China;Qingdao Municipal Centre for Disease Control and Prevention,Qingdao Institute of Prevention Medicine,Qingdao 266000,China;Henan Provincial Center for Disease Control and Prevention,Zhengzhou 450016,China)

机构地区：[1]中国疾病预防控制中心病毒病预防控制所,传染病溯源预警与智能决策全国重点实验室,国家卫生健康委医学病毒和病毒病重点实验室,北京102206 [2]解放军总医院第五医学中心,北京100039 [3]首都儿科研究所,北京100020 [4]陕西省疾病预防控制中心,西安710054 [5]长春市儿童医院,长春130051 [6]新疆维吾尔自治区疾病预防控制中心,乌鲁木齐830002 [7]中国检验检疫科学研究院卫生检验与检疫研究所,北京100123 [8]河北省疾病预防控制中心,石家庄050021 [9]湖南省疾病预防控制中心,长沙410005 [10]山东省疾病预防控制中心,济南250014 [11]重庆医科大学附属儿童医院,重庆400014 [12]青岛市疾病预防控制中心,青岛市预防医学研究院,青岛266000 [13]河南省疾病预防控制中心,郑州450016

出　　处：《病毒学报》2024年第1期13-26,共14页Chinese Journal of Virology

基　　金：十三五国家科技重大专项课题(项目号:2018ZX10713002),题目:病毒性传染病病原谱和病毒基因变异变迁规律研究;十三五国家科技重大专项课题(项目号:2018ZX10713001-003),题目:病毒性自然疫源性传染病症候群病原谱构成及流行规律研究;国家卫生健康委员会重大公共卫生专项(项目号:ZDGW21-131031103000180005),题目:中国疾控中心病毒病所腺病毒等4种重要病毒病原学监测网络的建立与运转。

摘　　要：为阐明我国全人群急性呼吸道感染(Acute respiratory infection,ARI)病例中人冠状病毒229E(Human coronavirus 229E,HCoV-229E)感染情况及病毒基因特征,本研究对2009-2021年间中国十一省份15,335例ARI监测病例中HCoV-229E核酸阳性病例进行描述性流行病学分析,同时对HCoV-229E阳性病例的临床标本进行S基因扩增和测序,阳性序列用于病毒系统发育和进化分析。本研究中共检测出316例HCoV阳性病例,其中38例为HCoV-229E阳性。HCoV-229E检出率在不同季节中差异无统计学意义(χ^(2)=2.345,P=0.504);男性检出率高于女性(χ^(2)=4.546,P<0.05);不同年龄组中,除了5~17岁青少年组未检测到HCoV-229E,其他年龄组间HCoV-229E检出率差异无统计学意义(χ^(2)=1.927,P=0.588)。在38例HCoV-229E阳性病例中有23例(60.53%)为混合感染病例,和HCoV-229E单一感染病例相比,包括肺炎病例在内的下呼吸道感染病例在混合感染病例中比例增高。本研究共获得9条2019-2021年HCoV-229E刺突蛋白(Spike protein,S)基因序列,结合从GenBank中下载的90条HCoV-229E S基因代表性序列共同构建系统发育树。结果表明,全球HCoV-229E序列可划分为Genogroup1~6共6个组,具有明显的时间聚集性。Genogroup 6是目前全球流行的主要优势谱系,位于HCoV-229E系统发育树的末端。本研究所获得的9条HCoV-229E序列均隶属于Genogroup 6,但位于不同分支。S基因分子进化速率约为7.32×10^(-4)替换/位点/年,S蛋白处于负向选择压力下(ω<1),但仍有个别正向选择位点存在,S蛋白多个位点上发生氨基酸突变和N-糖基化位点突变,其中部分突变发生在S蛋白受体结合结构域的3个受体结合环中。本研究通过开展中国内地部分地区ARI病例中HCoV-229E感染情况和病毒基因特征分析,阐述了我国HCoV-229E流行病学特征和病毒分子进化特点,为我国HCoV-229E感染的控制与预防提供基线数据。In order to the population‐based prevalence and viral genetic characteristics of Human coronavirus 229E(HCoV‐229E)infection among the cases with acute respiratory infection(ARI)in China,a descriptive epidemiological analysis of HCoV‐229E positive cases was conducted among 15,335 ARI cases in eleven provinces of China from 2009 to 2021.S gene amplification was performed on the clinical specimens obtained from HCoV‐229E‐positive cases for phylogenetic and evolutionary analysis.Among the 15,335 ARI cases,316 were identified to be positive for HCoV,with the detection rate of 2.06%.Of 207 cases identified for subtype,38 were confirmed to be positive for HCoV‐229E.The detection rate of HCoV‐229E exhibited no statistically significant differences across different seasons(χ^(2)=2.345,P=0.504).The detection rate of males is higher than that of females(χ^(2)=4.546,P<0.05).Among different age groups,except for the 5~17 age group where HCoV‐229E was not detected,no statistically significant differences in HCoV‐229E detection rate were observed(χ^(2)=1.927,P=0.588).Of the 38 HCoV‐229E positive cases,a total of 23(60.53%)were co‐infected cases,compared with HCoV‐229E single infection cases,the proportion of lower respiratory tract infection and pneumonia cases increased in co‐infection cases.Nine spike protein(S)gene sequences of HCoV‐229E were obtained from 2019 to 2021,and together with 90 HCoV‐229E S gene sequences downloaded from GenBank,a phylogenetic tree was constructed.The results indicated that HCoV‐229E worldwide could be classified into 6 genogroups,showing clear temporal clustering.The 9 HCoV‐229E S gene sequences all belong to genogroup 6 but occupied different clades,the genogroup 6 was also the predominant lineage worldwide and located at the end of the phylogenetic tree.The molecular evolution rate of the S gene is about 7.32×10^(‐4) substitutions/site/year.Most amino acid sites of the S protein are under negative selection pressure(ω<1),but there are still individual po

关 键 词：人冠状病毒229E 流行特征 系统发育分析 分子进化 

分 类 号：R373.1[医药卫生—病原生物学]