DHX15抗肠道病毒感染的功能和机制研究

肠道病毒感染能够在全世界范围内引起严重的胃肠炎和腹泻。据统计每年有超过600,000人因诺如病毒（norovirus）和轮状病毒（rotavirus）这两种常见肠道病毒感染而死亡，其中五岁以下儿童占绝大多数。鉴于此，阐明机体免疫系统和肠道病毒的相互作用对于预防和治疗肠道病毒感染有着非常重要的意义。我们之前的研究发现NLRP6可以通过招募DHX15发挥抗肠道病毒感染作用（science,2015）。为了验证DHX15的in vivo功能，我们制作了Dhx15条件性敲除小鼠。我们发现肠道上皮细胞特异性敲除DHX15的小鼠对肠道病毒感染更加易感，而且DSS诱导的肠炎明显加重。但是，DHX15识别的病毒种类和发挥作用的具体机制，以及DHX15在肠炎中的作用仍不清楚。本项目中我们将重点研究DHX15如何识别并抵御肠道病毒感染的功能和机制，并且如何维持肠道稳态的。

Enteric viruses are important etiological causes of severe gastroenteritis and dehydrating diarrhea worldwide. Norovirus and rotavirus, the two general enteric viruses, account for an annual death of more than 600,000 people, most of them being children under the age of five. Therefore, elucidating the interaction between enteric viruses and our immune systems will provide key insights into the immune mechanisms involved in host defense and immune-mediated diseases. Our previous results showed that NLRP6 played critical anti-viral role in the intestine by interacting with RNA helicase DHX15 (science, 2015). To validate the in vivo function of DHX15, we generated Dhx15 conditional KO mice. We found that mice with specific DHX15 deficiency in intestinal epithelial cells are more susceptible to enteric viral infection, and also showed more severe DSS-induced colitis phenotype. However, the roles and mechanisms of DHX15 in anti-enteric viral response and DSS-induced colitis are still not clear. In this project, we are going to investigate the role of DHX15 in anti-enteric virus response and the underlying mechanisms. We will further elucidate whether the colitis phenotype in Dhx15 f/f vil-cre mice is due to the lack of virus sensing pathway.