不同剂量DPP4转导后MERS-CoV感染小鼠模型的临床及生物学特征比较  

Clinical and Biological Character in Mouse Models for Middle East Respiratory Syndrome Generated by Transduction with Different Doses of DPP4 Molecule

作　　者：姚艳丰[1] 蓝佳明[2,3] 李枫棣[1] 牛培华 于品[1] 卢帅[2] 鲍琳琳[1] 谭文杰[2] 秦川[1] 

机构地区：[1]中国医学科学院,北京协和医学院,医学实验动物研究所,卫生部人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室 [2]中国疾病预防控制中心病毒病预防控制所,卫生与计划生育委员会医学病毒学与病毒病重点实验室,北京100021 [3]河北医科大学病原生物学教研室

出　　处：《病毒学报》2015年第6期593-600,共8页Chinese Journal of Virology

基　　金：传染病科技重大专项(2012ZX10004501;2014ZX10004001);973项目(2011CB504704);国家自然科学基金(31400787;81302607)

摘　　要：本研究探讨不同剂量DPP4转导小鼠后对中东呼吸综合征冠状病毒(Middle East respiratory syndrome coronavirus,MERS-CoV)感染建模及其生物特性的影响。首先将表达MERS-CoV受体DPP4的重组腺病毒以高剂量(2.5×108 PFU/只)、低剂量(0.5×108 PFU/只)分别转导转导BALB/c小鼠,继而滴鼻接种MERS-CoV,建立MERS-CoV感染小鼠模型。对成功构建的小鼠感染模型分别进行体征、病毒复制、免疫病理及抗体应答的比较分析。结果表明:两种剂量DPP4转导后MERS-CoV感染小鼠,均可引起典型肺炎表征,在小鼠肺部能检测到病毒复制及免疫病理,但高剂量DPP4转导组小鼠肺炎体征与肺病理损伤更明显,病毒复制水平亦高于低剂量DPP4转导组。小鼠感染建模后2w后可检测到结构蛋白特异抗体与中和抗体,高剂量DPP4转导组抗体应答亦明显高于低剂量转导组。本研究以两种剂量DPP4转导小鼠,均成功建立了MERS-CoV感染的小鼠模型,受体DPP4转导水平可影响MERS-CoV感染小鼠体征、病毒复制及抗体应答。In this study,we evaluated the difference of biological characteristics in the MERS-CoV infected mice model in prior to transduction with different dosage of human DPP4.Firstly,we transduced different dosage of DPP4（high or low）into mice,and then challenged them with MERS-CoV in order to establish the model.After establishment of mice model,we observed the clinical signs of disease,virus replication,immunopathogenesis and antibody response.The results indicated that the infected mice showed typical pneumonia,virus replication,histological lesions,and neutralizing antibody production.Moreover,the high dosage group was superior to the low dosage group.Fourteen days after infection,the specific antibody to virus structural protein and neutralizing antibody were analyzed,the high dosage group induced higher level antibody.In summary,the MERS-CoV infected mice model were established prior transduction with DPP4,and the level of DPP4 influenced the clinical signs of disease,virus replication and antibody response in this model.

关 键 词：中东呼吸综合征 中东呼吸综合征冠状病毒 动物模型 小鼠 抗体应答 

分 类 号：R373.9[医药卫生—病原生物学]