猪流行性腹泻病毒调控外周血CD4+T细胞靶向小肠黏膜迁移的机制研究

近年来猪流行性腹泻病毒（PEDV）的频发给我国养猪业造成了巨大的经济损失。申请人前期发现，PEDV经仔猪鼻腔黏膜入侵后，能感染外周血CD4+T细胞，并通过促进其向小肠黏膜迁移引起肠道感染。进一步探索发现，PEDV可能通过影响CD4+T细胞归巢受体整合素α4β7调控其靶向小肠黏膜迁移，但潜在的机制尚不明确。因此，本项目拟开展以下研究：1）研究PEDV对猪外周血CD4+T细胞整合素α4β7表达的影响，并探究病毒通过膜蛋白（M）调控整合素α4β7转录的机制；2）探明整合素α4β7在PEDV促进CD4+T细胞向仔猪小肠黏膜迁移中的作用；3）解析PEDV通过整合素α4β7-Rho-GTPase信号途径调控CD4+T细胞伪足形成，促进其归巢至小肠淋巴组织后，向小肠黏膜迁移的分子机制。本研究将重点阐明PEDV经鼻入侵后，通过调控CD4+T细胞迁移感染仔猪肠道的致病机理，为有效防控PEDV提供理论依据。

The frequently emerged of porcine epidemic diarrhea virus (PEDV) in China has caused major economic losses to pig industries. Our previous studies proved that the nasal mucosal invasion PEDV can infect CD4+T in peripheral blood, and cause intestinal infection by promoting virus-loaded CD4+T cells migrating to intestinal mucosa. Further studies found that PEDV may regulate CD4+T cells migration by affecting the expression of homing receptor integrin α4β7, while the involved mechanism was remained unclear. Therefore, the following experiments will be performed. (1) Study the effect of PEDV on the expression of integrin α4β7 in CD4+T cells from piglet’s peripheral blood, and explore the mechanism involved in the transcription of α4β7 stimulated by membrane (M) protein of PEDV; (2) Study the role of integrin α4β7 in PEDV induced intestinal specific migration of peripheral blood CD4+T cells; (3) Clarify the molecular mechanism by which PEDV promote intestine homing CD4+T cells formed cellular pseudopods for migrating to small intestinal mucosa, via stimulating α4β7-Rho-GTPase signaling pathway. Our study aimed to further elucidate the mechanism by which nasal invasion PEDV caused intestinal infection through affecting the migration of virus loaded CD4+T cells, hoping to lay a theoretical foundation for effective control and prevention of PEDV.