LSUHSC COBRE: NOROVIRUS IMMUNITY AND PATHOGENESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 子项目1：淋巴组织持续感染诺沃克病毒损害保护性免疫 斯蒂芬妮·M·卡斯特 杯状病毒科中的人类诺如病毒是世界范围内非细菌性胃肠炎暴发的主要原因，也是公共卫生关注的新病原体。该项目的主要目标是设计合理的疫苗接种战略，以防止诺沃克病毒感染。人类诺沃克病毒感染不能诱导持久免疫，这可能是疫苗设计的一个非常重要的观察结果。我们现在概述了这种非典型的免疫模式，在小鼠模型中，MNV-1原发感染小鼠未能引发记忆免疫反应，从而保护小鼠免受粘膜感染或疾病。我们小组和其他人积累的证据表明，诺如病毒导致淋巴组织的持续感染。我们最初的假设是，淋巴间隔中持续的病毒复制会损害保护性免疫反应的产生。然而，我们现在已经确定，第二个小鼠诺沃克病毒株MNV-3，它持续感染小鼠的时间比MNV-1实际上诱导保护性免疫的时间更长。因此，MNV持续感染的持续时间与主要挑战提供的保护程度之间似乎没有直接的相关性。有趣的是，保护性免疫诱导和细胞趋向性之间存在相关性。因此，我们假设MNV感染粘膜抗原提呈细胞损害了保护性记忆免疫的发展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Subproject #1: Persistent norovirus infection of lymphoid tissue impairs protective immunity Stephanie M. Karst Human noroviruses in the Caliciviridae family are the major cause of nonbacterial gastroenteritis outbreaks worldwide and are emerging pathogens of public health interest. The major goal of this project is to design rationale vaccination strategies to prevent norovirus infection. Human norovirus infection does not induce lasting immunity, potentially a very important observation in terms of rationale vaccine design. We have now recapitulated this atypical pattern of immunity in the mouse model  primary MNV-1 infection of mice fails to elicit memory immune responses that protect from mucosal infection or disease. Accumulating evidence by our group and others demonstrates that noroviruses cause persistent infection of lymphoid tissues. We initially hypothesized that persistent viral replication in lymphoid compartments impairs the generation of protective immune responses. However, we have now determined that a second murine norovirus strain, MNV-3, which persistently infects mice for a longer duration than does MNV-1 actually elicits protective immunity. Thus, there does not appear to be a direct correlation between the length of persistent MNV infection and the magnitude of protection afforded by a primary challenge. Interestingly, there is a correlation between protective immunity induction and cell tropism. We therefore hypothesize that MNV infection of mucosal antigen presenting cells impairs the development of protective memory immunity.