EV71和CA16型手足口病动物模型及其病毒感染特点分析

Animal Models of EV71 and CA16 Hand-foot-mouth Disease and Characteristics of Viral Infection

手足口病(HFMD)是由肠道病毒引起的儿童常见传染病,发病率高,可引发肺水肿、心肌炎、无菌性脑膜炎等致命性并发症,严重威胁着患儿的健康。目前该病相关病毒的致病机制、致病病毒不同基因型之间的关系、药效学评价方法、药物抗病毒机制等核心问题尚不明确,而构建具有人类染毒模拟表现的动物模型是解决以上问题的关键。国内外研究人员建立了多种不同动物种属、品系的HFMD动物模型,以肠道病毒71型(EV71)和柯萨奇病毒A16型(CA16)最常见,应用也最为广泛。EV71与CA16同属小核糖核酸病毒科肠道病毒属肠道病毒A型,两者在病原学、感染和复制特征、感染导致的临床症状和免疫反应有相似的方面,但引发的HFMD动物模型在易感年龄,感染方法,表现出的神经毒性、临床症状及体征、组织器官损伤程度等也有明显不同的方面,因此,研究者应根据实际需要选择和建立合适的动物模型,这对于研究结果的可靠性具有重要意义。本文通过梳理感染EV71和CA16病毒建立的不同物种HFMD动物模型,分类阐述各模型的种属品系、病毒株类型、感染方法、病毒感染特点,深入研究EV71及CA16感染诱发的HFMD特点及其感染所导致的临床症状差异,整体评价小鼠、树鼩及非人灵长类3类动物模型各自的优缺点,以期为相关研究提供参考。

Hand-foot-mouth disease( HFMD) is a common infectious disease caused by enterovirus in children. It has a high incidence and can cause fatal complications such as pulmonary edema,myocarditis and aseptic meningitis,seriously threatening the health of children. At present,some core problems such as the pathogenesis of disease,the relationship between different genotypes of pathogenic viruses,the pharmacodynamic evaluation methods,and the antiviral mechanism of drugs are still unclear. The construction of disease animal models with simulation performance of human exposure is the key to solve the above problems. Researchers both at home and abroad have established a variety of animal models for HFMD,of which enterovirus 71( EV71) and coxsackievirus A16( CA16) are most common and most widely used. Both EV71 and CA16 are enterovirus A in picornavirus family,so they have similarities in terms of pathogenicity,infection and replication characteristics,clinical symptoms caused by infection and immune response,but also have significant differences in age of susceptibility,method of infection,as well as neurotoxicity,clinical symptoms and signs,and degree of tissue and organ damage. Therefore,researchers shall select and establish proper animal models based on actual conditions,which is critical to the reliability of the results. In this paper,the different types of HFMD animal models established by EV71 and CA16 viruses were reviewed,especially on the species strains,virus strain types,infection methods,and characteristics of viral infections in each model,and the characteristics and clinical symptoms of HFMD induced by EV71 and CA16 were also investigated to provide reference for related research.