Regulation of enterovirus A71 infection by tumor suppressor WW domain-containing oxidoreductase

• Main Authors: Pei-ShiuanChen, 陳佩璇
• Other Authors: Li-Jin Hsu
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/06946807235120773817

碩士 === 國立成功大學 === 醫學檢驗生物技術學系 === 104 === Human fragile WWOX gene encodes a tumor suppressor WW domain-containing oxidoreductase (designated WWOX). WWOX protein has been shown to regulate embryonic development, bone metabolism, neural injury and apoptosis through various signaling pathways. Previous studies have suggested that WWOX interacts with EB virus latent membrane protein 2A and HTLV-1 oncoprotein Tax, thus leading to tumorigenesis. However, whether WWOX affects viral infection remains unknown. Enterovirus A71 (EV-A71) belongs to the Enterovirus genus within the family of Picornaviridae. In this study, we found that Wwox-/- mice showed higher mortality rates and clinical scores as compared with Wwox+/+ and Wwox+/- littermates after intraperitoneal or oral infection of EV-A71. Higher viral loads were detected in multiple organs of EV-A71-infected Wwox-/- mice. These results suggest that WWOX may downregulate EV-A71 infection in vivo. To investigate how host factor WWOX downregulates EV-A71 infection, we examined EV-A71 life cycle in WWOX-knockdown cell lines. In summary, our results suggest that WWOX negatively regulates EV-A71 infection both in vivo and in vitro. In the future, WWOX-mediated signaling pathways that regulate EV-A71 infection will be further investigated.