为建立Cox.A16型手足口病乳鼠动物模型并进行免疫、致病特性研究.将临床分离的Cox.A16病毒株经蚀斑纯化,乳鼠驯化,最终获得1株能致死11日龄乳鼠的Cox.A16毒株,命名为TS10/08 (GenBank Accession NO.JX068829,Cox.A16-TS).Cox.A16-TS感染11日龄C57BL/6J乳鼠后,观测临床疾病得分、体质量变化、死亡率并测定病毒载量、免疫分子、组织病理损伤等病毒、免疫、病理指标.结果表明,Cox.A16-TS毒株感染11日龄C57BL/6J乳鼠,其病毒毒力为50 LD50/mL,感染后不同时期肌肉病毒载量均高于其他组织中,至4d达到高峰,后不断下降.至感染后6d发病达高峰时做病理检测,相对于脑组织,肌肉中有更严重的淋巴细胞浸润,引起更严重的炎性分子升高.血清中MCP-1,MIP-1alpha,MIP-1beta和CSF3动态变化,并在不同时间形成峰值.本试验初步建立了Cox.A16型手足口病乳鼠动物模型,为药物筛选、疫苗研发和免疫机理研究奠定了基础.

Coxsackievirus group A type 16(CVA16) is one of major pathogens which usually induces hand,foot and mouth disease(HFMD) and occasionally makes lethal complications.Recently,HFMD has broken out in the Asia-Pacific region,it becomes a major public health problem.We review the biological characteristics,clinical manifestations,and epidemiological characteristics of CVA16,and laboratory diagnosis as well as medical treatment for HFMD caused by CVA16,which may contribute to the control and prevention of HFMD.

Enterovirus 71(EV71) is a major causative agent of epidemics of hand-foot-mouth disease which associates with severe neurological disease,but the mechanism of EV71 pathogenesis remains unknown.In this study,we aimed to construct EV71 infected suckling mouse model and to evaluate immunological,endocrinological,and pathological characteristics of this model.In order to construct EV71 infected suckling mouse model,the clinical isolates of EV71 were purified by plaque purification,adapted to 3T3 cells,and then used infected suckling mice.EV71-BJ strain(GenBank accession NO.JQ319054) was finally achieved,which can make 7-day-old suckling mice infection and death.After the 7-day-old suckling mice were infected,we observed the clinical disease scores,body weight changes,and mortality.On 6 days post infection,viral loads of the brains and muscles,immune molecule levels,endocrine hormone levels,and pathological damages of the brains and muscles were determined by real-time RT-PCR,cytometric bead array(CBA),ELISA and histopathology,respectively.The virulence of EV71-BJ for 7-day-old suckling mice was 150 LD50/ml.The viral loads in muscles,with a peak on day 4 postinfection,were higher than that in brain.On 6 days post infection,more severe necrotizing myositis and infiltration of lymphocytes were observed in the mice muscles,with more significant rise of MCP-1,IFN-γ,IL-6 and TNF-α,compared with that of the mouse brains.However,no significant changes of epinephrine and cortisol were observed in the infected mice.In conclusion,an EV71 infected mouse model has been established,which will serve medicine screening,vaccines development and immunopathology researches for EV71 infection.