LSUHSC COBRE: NOROVIRUS IMMUNITY AND PATHOGENESIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 子项目#1：淋巴组织持续性诺如病毒感染损害保护性免疫 斯蒂芬妮·M岩溶 杯状病毒科中的人诺如病毒是全球非细菌性胃肠炎暴发的主要原因，并且是公共卫生关注的新兴病原体。本计画的主要目的是设计合理的疫苗接种策略以预防诺如病毒感染。 人诺如病毒感染不会诱导持久的免疫力，这可能是疫苗设计原理方面非常重要的观察结果。 我们现在已经在小鼠模型中概括了这种非典型的免疫模式  小鼠的原发性MNV-1感染不能引发保护免受粘膜感染或疾病的记忆免疫应答。 我们小组和其他人积累的证据表明，诺如病毒引起淋巴组织的持续感染。 我们最初假设，持续的病毒复制在淋巴区室损害保护性免疫反应的产生。 然而，我们现在已经确定了第二种鼠诺如病毒株MNV-3，其持续感染小鼠的持续时间比MNV-1更长，实际上增强了保护性免疫。 因此，持续MNV感染的时间长短与初次攻毒提供的保护程度之间似乎没有直接相关性。 有趣的是，保护性免疫诱导和细胞嗜性之间存在相关性。 因此，我们假设MNV感染粘膜抗原呈递细胞损害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.