GSE96586
Murine Norovirus Infection Initiates Interferon and TNF Signaling with Significant Alteration of Lipid and Cell Cycle Homeostasis
Murine norovirus (MNV) is genetically similar to human norovirus (HuNoV), and offers both an efficient in vitro cell culture system and animal model by which to investigate the molecular basis of replication.  Here, we present a detailed global view of the cellular alterations that occur during the progression of a norovirus infection. The transcriptome of a synchronously infected population of MNV-infected murine macrophage-like cell line (RAW264.7) was determined at 8, 14, and 20 hours post infection. The cellular genetic response was analyzed both globally and by specific pathways. Viral replication was monitored by RNA-seq and quantitative real-time PCR in context of the cellular phenotypic response.  The majority of transcriptionally up regulated genes were related to the IFN response. Additionally, there was a global increase in gene transcripts associated with immune response and inflammation. A transcriptional decrease was observed across many cellular processes, but particularly for genes involved in lipid homeostasis and cell cycle. The peak of the transcriptional immune response correlated with detected viral genome copies and changes in cellular phenotype including nuclear condensation. A more complete understanding of host response to norovirus infection will help to highlight the cellular pathways critical for a more effective immune response as well as those that may be exploited by the virus for therapeutic development. Overall design: Time course study of murine macrophage-like cell line gene expression infected with Murine nororvirus.