EV-A71和CV-A16感染正常人呼吸道上皮细胞诱导差异性IFN-I产生通路相关基因表达的研究  

Expression of Type-ΙInterferon Production Pathway-Related Genes Induced by Infection Due to Enterovirus 71 or Coxsackievirus A16 in Normal Human Airway Epithelial Cells

作　　者：宋杰[1] 胡雅洁[1] 李嘉祺[1] 王晶晶[1] 郭磊[1] 郑惠文[1] 宁若彤 王丽春[1] 李琦涵[1] 刘龙丁[1] 

机构地区：[1]中国医学科学院北京协和医学院医学生物学研究所云南省重大传染病疫苗研发重点实验室,昆明650118

出　　处：《病毒学报》2016年第6期694-701,共8页Chinese Journal of Virology

基　　金：国家自然科学基金面上项目(项目号:81373142);题目:肠道病毒71型感染相关的免疫分子转录组学研究;云南省科技计划项目生物重大科技专项(项目号:2015GA010);题目:EV71-CoxA16联合疫苗的研究及其他疫苗研究

摘　　要：手足口病(hand,foot and mouth disease,HFMD)是一种全球性的传染病,其主要病原体为肠道病毒A组71型(Enterovirus group A 71,EV-A71)和柯萨奇病毒A组16型(cosackievirus A 16,CV-A16)。EV-A71感染易引发重症病例及死亡病例,而CV-A16感染所致的症状普遍较轻,且CV-A16容易引发重复感染,但目前其中的机理仍不清楚。本研究比较了EV-A71与CV-A16感染正常人呼吸道上皮细胞16HBE后I型干扰素(Type I interferon,IFN-Ι)产生相关基因的改变。结果发现EV-A71感染后TLR3、TLR7、RIG-I、MDA5、MAVS、MyD88、IRF3、IRF7、IFNα和IFNβ的基因表达量均发生了显著性地上调,而在CV-A16感染后仅MDA5显著性上调;TLR3和IRF3的基因表达水平显著性地下降,而其它基因表达水平均无显著性地变化。此外,病毒滴度和病毒拷贝数的检测结果显示,CV-A16在16HBE上的复制效率明显高于EV-A71。上述结果提示我们EV-A71和CV-A16感染16HBE对其IFN-I产生相关基因表达的影响完全不一样,且CV-A16更容易感染人呼吸道上皮细胞。本研究为EV-A71和CV-A16引起的临床症状差异的机理研究以及CV-A16重复感染的机理研究提供了线索。Hand,foot,and mouth disease（HFMD）is caused by mainly enterovirus 71（EV-A71）and coxsackievirus A16（CV-A16）,and is a serious healthcare problem worldwide.EV-A71 infection is thought to progress readily to serious complications whereas CV-A16 infection,in general,results in mild symptoms and presents repeatedly.However,the underlying mechanisms leading to these differences are not known.We compared changes in expression of type-I interferon（IFN-I）-related genes in normal human bronchial epithelial（16HBE）cells.Geneexpression levels of TLR3,MAVS,MDA5,MyD88,IRF7,IFNαand IFNβwere elevated significantly after EVA71 infection.MDA5expression was increased markedly,and that of TLR3 and IRF3was decreased obviously after CV-A16 infection,but that of MAVS,MyD88,IFNαand IFNβdid not show significant differences.Viral copy number and viral titers suggested that CV-A16 replicates more efficiently than EV-A71 in 16HBE.These results suggest that IFN-I production pathway-related genes in response to infection by EV-A71 and CV-A16 have notable discrepancies.Such information could shine a light on the different manifestations caused by EV-A71 and CV-A16,and the mechanism of repeat infection by CV-A16.

关 键 词：手足口病 肠道病毒A组71型(EV-A71) 柯萨奇病毒A组16型(CV-A16) 呼吸道上皮细胞 干扰素 

分 类 号：R373.2[医药卫生—病原生物学]