Project description:To investigate whether and what miRNAs expression might be regulated by VSV (vesicular stomatitis virus?) challenge, we analyzed the miRNA expression profile of mouse primary peritoneal macrophages infected with VSV by using an array-based miRNA profiling. After the infection of VSV at MOI 10 for 48 h, the array revealed that many miRNAs were up-regulated in macrophages?
Project description:Our findings demonstrated that BCG treatment significantly reduced the intracellular viral titers of Vesicular Stomatitis Virus (VSV). To explore the molecular mechanisms responsible for the enhanced antiviral immunity of BCG-trained macrophages, we conducted RNA sequencing analysis on RAW264.7 cells infected with VSV, comparing macrophages pre-exposed to BCG with those without prior exposure.
Project description:Sarm-deficient mice are protected from VSV encephalitis and death. Microarray was done to examine genes contributing to this phenotype WT and KO mice were infected with VSV and brains were harvested at day 5 post-infection for RNA extraction
Project description:Sarm-deficient mice are protected from VSV encephalitis and death. Microarray was done to examine genes contributing to this phenotype
Project description:Heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved in many processes in RNA metabolism. In addition to their functions in the nucleus, hnRNPs can function in the replication of RNA viruses in the cytoplasm. In vesicular stomatitis virus (VSV)-infected cells, several hnRNPs relocalize from the nucleus to the cytoplasm. This raises the question of whether these hnRNPs are relocalized together with their host nuclear RNAs or whether they associate with new RNAs in the cytoplasm. hnRNP A1, hnRNP C1/C2, and hnRNP K were immunoprecipitated from mock- or VSV-infected cells, and RNAs were analyzed by high content RNA sequencing. Each hnRNP displayed a loss of interaction with cellular transcripts in favor of viral mRNAs. hnRNP A1 was preferentially associated with VSV phosphoprotein (P) mRNA; hnRNP C1/C2 was preferentially associated with VSV glycoprotein (G) mRNA, and hnRNP K bound viral transcripts in rank of abundance.
Project description:The lack of tumor-specific targeting by oncolytic viruses (OVs) restricts their therapeutic potential. Here, we report a “cap-linker” strategy to modify the vesicular stomatitis virus (VSV) glycoprotein (G protein, VSV-GIN). The modified VSV (Pro-VSVIN) loses its ability to infect cells until present in the tumor microenvironment, where the linker is cleaved by tumor-enriched matrix metalloproteases (MMPs). When Pro-VSVIN is armed with a single-chain IL-12 (Pro-VSVIN-IL-12) and systemically injected into MC38 tumor-bearing mice, Pro-VSVIN-IL-12 shows a markedly improved safety profile and eradicates tumors. The efficacy of Pro-VSVIN-IL-12 was further improved when combined with PD-1 checkpoint blockade. Compared to WT VSVIN that carries IL-12, intravenously injected Pro-VSVIN-IL-12 leads to strong Th1 immunity, near abolishment of regulatory T cells, and CD8+ T cell activation in tumors. This preclinical work demonstrates a new tumor-specific targeting strategy of VSV for enhanced immunotherapy safety with superior efficacy.