Cellular Immunology of Enterovirus Infection

描述（由申请人提供）：小核糖核酸病毒家族的成员导致人类和其他动物物种中的多种疾病。虽然小核糖核酸病毒的复制通常是很好的理解，小核糖核酸病毒感染引起的细胞免疫机制知之甚少。科萨基B病毒（CVB）是肠道病毒属小核糖核酸病毒的成员。提出的研究的总体目标是使用肠内和胃肠外感染的小鼠模型来表征由CVB感染引起的细胞免疫应答的广度和幅度。具体目的是量化和表征口服接种后引起的CD 4和CD 8 T细胞应答，并将其与胃肠外感染引起的细胞免疫应答进行比较。这些实验将采用经工程改造以表达淋巴细胞性脉络丛脑膜炎病毒（LCMV）表位的重组CVB变体，以及表达特异性LCMV特异性TCR变体的转基因小鼠。这些研究将为进一步研究小核糖核酸病毒病的宿主-病原体关系以及小核糖核酸病毒作为肠内递送疫苗载体的潜在效用提供基础。

DESCRIPTION (provided by applicant): Members of the picornavirus family are responsible for a wide variety of diseases among humans and other animal species. While the replication of picornaviruses is generally well understood, little is known about cellular immune mechanisms elicited by picornavirus infection. Coxsackie B virus (CVB) is a member of the enterovirus genus of picornaviruses. The general goal of the studies proposed is to characterize the breadth and magnitude of cellular immune responses elicited by CVB infection, using murine models of enteral and parenteral infection. The specific aims are to quantify and characterize CD4 and CD8 T cell responses elicited following oral inoculation, and to compare these to cellular immune responses elicited by parenteral infection. These experiments will employ recombinant CVB variants engineered to express lymphocytic choriomeningitis virus (LCMV) epitopes, and transgenic mice that express a specific LCMV specific TCR variant. These studies will provide a foundation for further studies of host-pathogen relationships in picornavirus disease and the potential utility of picornaviruses as enterally delivered vaccine vectors.