REPLICATION OF NOROVIRUSES IN CELL CULTURE

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。 虽然诺如病毒(NIAID B类优先病原体)能够引起急性胃肠炎的大规模暴发，是一个主要的公共卫生问题，但缺乏细胞培养系统极大地阻碍了预防措施的研究，如疫苗和抗病毒药物的开发。这个应用程序的长期目标是了解诺如病毒的复制。我们最近开发的基于细胞的新型诺沃克病毒复制系统(诺沃克病毒复制子携带细胞)将用于研究诺沃克病毒的复制和抗病毒药物。我们将特别关注IFN对NV复制的影响。我们计划使用不同的诺沃克病毒株来产生更多的诺沃克病毒复制子携带细胞，采用与携带NV复制子的细胞相似的策略，寻找在细胞中有效复制的菌株。由于我们发现胆汁酸和胆固醇途径在相关病毒猪肠道杯状病毒(PEC)的细胞培养中起重要作用，我们将检测诺如病毒复制过程中的胆汁酸/胆固醇途径。具体地说，我们将检测胆汁酸的法尼类X受体(FXR)和G蛋白偶联受体(TGR5)在诺如病毒复制中的作用。这些研究应有助于在细胞培养中分离诺如病毒，这是制定预防策略以控制诺如病毒引起的腹泻疾病的关键。

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. Although noroviruses (NIAID category B priority pathogen) are a major public health concern with their ability to cause large outbreaks of acute gastroenteritis, the lack of a cell culture system greatly hinders research on preventive measures, such as the developments of vaccines and antiviral drugs. The long term goal of this application is to understand the replication of noroviruses. Novel cell based norovirus replication system (Norwalk virus [NV] replicon-bearing cells), which we developed recently, will be used for studying replication and antivirals of noroviruses. Especially we will focus on the effects of IFNs on the replication of NV. We plan to generate additional norovirus replicon-bearing cells using different norovirus strains adapting the similar strategy for that of NV replicon bearing cells in searching for strains efficiently replicate in cells. Because we found the bile acids and cholesterol pathways were important in growing the related virus, porcine enteric calicivirus (PEC) in cell culture, we will examine bile acids/cholesterol pathways in the replication of norovirus. Specifically, we will examine farnesoid X receptor (FXR) and G protein couple receptor (TGR5) of bile acids in the replication of norovirus. These studies should contribute to the isolation of noroviruses in cell culture, which is a key for development of preventive strategies to control diarrheal disease caused by noroviruses.