This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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 in cell culture system. Novel cell based norovirus replication system (Norwalk virus [NV] replicon bearing cells), which we developed recently, will be used for studying the effects of interferons (IFNs, type I and II) to elucidate the detailed role of IFNs in 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 enabled to grow the related virus, porcine enteric calicivirus (PEC) in cell culture, we will examine bile acids in the replication of norovirus. Specifically, we will examine bile acid mediated signaling pathways via bile acid receptors such as farnesoid X receptor (FXR) and G protein couple receptor (TGR5) in the replication of norovirus in associated with IFN system. 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.
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