Evaluation of the role of H-Ras in the regulation of RLR signaling pathway

• Main Authors: Guann-An Chen, 陳冠安
• Other Authors: Lih-Hwa Hwang
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/b985gk

博士 === 國立陽明大學 === 微生物及免疫學研究所 === 106 === We have used shRNA high-throughput screening method to screen for the unrevealed potential cellular factors involved in antiviral responses, and identified a proto-oncogene, H-Ras, acting as a positive regulator in antiviral activity, whose depletion could enhance Sindbis virus and vesicular stomatitis virus replication. Further analyses indicated that depletion of H-Ras results in a decrease in Sendai virus (SeV)-induced retinoic acid-inducible gene-I-like receptor (RLR) signaling. Interestingly, however, ectopic expression of wild-type H-Ras results in a biphasic mode of RLR signaling regulation: while low-level expression of H-Ras enhances SeV-induced RLR signaling, high-level expression of H-Ras significantly inhibits this signaling. The inhibitory effects correlate with the activation status of H-Ras. Mechanistically, we demonstrate that depletion of H-Ras reduces the formation of MAVS/TRAF3 signaling complexes and oncogenic H-Ras exerts a negative effect on type I IFN (IFN-I) responses. In summary, we have proven the role of H-Ras in the regulation of type I interferon responses; however, the detailed mechanisms remain to be further investigated.