Utilizing endogenous microRNA-155 to study pathogenic role of Japanese encephalitis virus in immune cells of the infected mice

• Main Authors: chi-cheng Lin, 林積成
• Other Authors: 廖經倫
• Format: Others
• Language: zh-TW
• Published: 105
• Online Access: http://ndltd.ncl.edu.tw/handle/51712609637346969964

碩士 === 國防醫學院 === 微生物及免疫學研究所 === 98 === MicroRNAs (miRNAs) are endogenous non-coding RNAs that spatiotemporally modulate mRNAs in a post-transcriptional manner. The engineering of viruses by insertion of a tissue-specific miRNA recognition element (MRE) into viral mRNA can restrict viral tissue tropism. In this study we employed Japanese encephalitis virus (JEV) to investigate whether immune-enriched miRNAs are able to suppress JEV replication through the targeting of its nonpolyadenylated viral mRNA. Myeloid cells such as macrophages and dendritic cells are the primary targets for JEV infection; thus, likely contributing to viral pathogenesis. Expression of miR-155 can be enhanced in dendritic cells, macrophages/monocytes, B-cells and T-cells especially by inflammatory signals through Toll-like receptors upon exposure to antigen or by interferon stimulation. To create an immune cells-restricted JEV, we inserted MRE of miR-155 into the 3′-untranslated region (3′-UTR) of viral genome, and investigate whether endogenous miR-155 can diminish virulence of this recombinant JEV in the infected mice. This approach may not only allow us to study JEV pathogenesis involved particularly in viral tissue tropism but also provide an additional layer of biosafety, and thus having great potential for rational development of safer flavivirus vaccine。