REPLICATION OF NOROVIRUSES IN CELL CULTURE

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。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他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。 虽然诺如病毒（NIAID B类优先病原体）是一个主要的公共卫生问题，其能够引起急性胃肠炎的大爆发，但缺乏细胞培养系统极大地阻碍了预防措施的研究，例如疫苗和抗病毒药物的开发。本申请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诺如病毒复制系统（诺沃克病毒[NV]复制子承载细胞）将用于研究诺如病毒的复制和抗病毒药物。特别是，我们将集中在干扰素对NV复制的影响。我们计划使用不同的诺如病毒株产生额外的携带诺如病毒复制子的细胞，采用与携带NV复制子的细胞相似的策略来寻找在细胞中有效复制的病毒株。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）的细胞培养中的生长中是重要的，因此我们将研究诺如病毒复制中的胆汁酸/胆固醇途径。具体而言，我们将研究法尼醇X受体（FXR）和G蛋白偶联受体（TGR 5）的胆汁酸在诺如病毒的复制。这些研究将有助于在细胞培养中分离诺如病毒，这是发展控制诺如病毒引起的呼吸道疾病的预防策略的关键。

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.