人源和禽源H7N9亚型禽流感病毒遗传进化分析及对小鼠的毒力评估  

Genetic Analysis and Virulence of H7N9 Influenza A Viruses Isolated from Chickens and Humans in Mice

作　　者：郭晶[1,3] 夏瑜[2] 杨佳欣[1] 张晓璇 高鑫鑫 刘成 李旭勇[1] GUO Jing;XIA Yu;YANG Jia-xin;ZHANG Xiao-xuan;GAO Xin-xin;LIU Cheng;LI Xu-yong(College of Agricultural,Liaocheng University,Liaocheng,Shandong,252000,China;Suzhou Center for Disease Prevention and Control,Suzhou,Jiangsu,215000,China;State Key Laboratory of Veterinary Biotechnology,Harbin Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Harbin,Heilongjiang,150069,China)

机构地区：[1]聊城大学农学院,山东聊城252000 [2]苏州市疾病预防控制中心,江苏苏州215000 [3]中国农业科学院哈尔滨兽医研究所兽医生物技术国家重点实验室,黑龙江哈尔滨150069

出　　处：《动物医学进展》2020年第12期40-46,共7页Progress In Veterinary Medicine

基　　金：国家自然科学基金项目(31702261、31702262);山东省自然科学基金项目(ZR2017BC057、ZR2017BC048);2017年苏州市科技局产业技术创新专项(SYS201780);兽医生物技术国家重点实验室开放基金项目(SKLVBF201906)。

摘　　要：新型禽源A型H7N9禽流感病毒一直威胁着人类健康,对病毒的遗传进化和生物学特性进行持续研究对于H7N9禽流感的防控十分重要。为了解导致禽类和人类感染的H7N9病毒的进化、突变及其生物学特性,2014年和2015年从中国江苏分离出1株禽源和2株人源H7N9病毒,分别对这3株病毒的进化进行了评估。序列分析显示,HA基因在核苷酸水平上有98.7%至99.5%的同源性,并聚集成两个系统发育群。3株病毒的6个内部基因在核苷酸水平上具有96.8%至99.6%的同源性。在2株人源分离株的PB2中有E627K氨基酸位点突变,且在血凝素(HA)切割位点无连续碱性氨基酸插入。动物试验表明,人源分离株SZ19在小鼠中的毒力比禽源分离株CK/SZ141高,接种了SZ19病毒的小鼠体重下降了18%。此外,在观察期间2株试验病毒均未致死小鼠。病理学研究结果显示,与禽源病毒相比,人源H7N9病毒更容易感染小鼠的上呼吸道和下呼吸道。试验结果提示对禽类和人类进行H7N9禽流感系统监测的重要性以及在哺乳动物模型中对H7N9病毒的复制和致病性进行系统评估的必要性。Novel avian origin influenza A(H7N9)viruses were first detected in 2013 and continue to pose a threat to poultry and human health.Although H7N9 outbreaks of both avian and human influenza infections have significantly declined since the compulsory immunization of poultry with the H7N9 vaccine in 2017,continuous study on genetic evolution and biological characteristics of the viruses were necessary for prevention and control of H7N9 influenza.In order to understand the evolution and mutation of H7N9 viruses and their biological properties which contribute to avian and human infectious diseases.We evaluated the evolution of one avian and two human H7N9 viruses isolated in 2014 and 2015 from Jiangsu province.Sequencing results showed that the HA genes were 98.7%to 99.5%identical at the nucleotide level and clustered into two phylogenetic groups.The six internal segments from our three test viruses were 96.8%to 99.6%identical at the nucleotide level.The two human isolates possessed E627K mutations in the PB2 gene and with no amino acids insertion at the hemagglutinin(HA)cleavage site.Animal studies indicated that the human isolate SZ19 was more virulent in mice than the avian isolate CK/SZ141.The body weights of mice infected with the SZ19 virus decreased 18%.In addition,neither virus produced any mouse lethality during the observation period.The pathological studies showed that the human H7N9 virus was better adapted to the upper and lower respiratory tracts in mice than the chicken virus.Our results highlight the need for a systematic H7N9 influenza surveillance of birds and humans and to systematically evaluate replication and pathogenicity of H7N9 viruses in mammalian models.

关 键 词：H7N9禽流感病毒 进化 毒力 小鼠 

分 类 号：S852.657[农业科学—基础兽医学] S865.13[农业科学—兽医学]