IFN-stimulated P2Y13 protects mice from viral infection by suppressing the cAMP/EPACl signaling pathway
作者机构：Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241 China
出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)
年 卷 期：2019年第11卷第5期
页 面：395-407页
核心收录：
学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 07[理学] 1001[医学-基础医学(可授医学、理学学位)]
基 金：the National Key R&D Program of China (2018YFA0507000 to B.D.) the National Natural Science Foundation of China (31570896 and 31770969 to B.D., 81672811 to M.Q.) Joint Research Institute for Science and Society (JoRISS)(14JORISS01 to B.D.) Science and Technology Commission of Shanghai Municipality (15JC14O15OO to B.D.) Innovation Program of Shanghai Municipal Educati on Commissi on (2017-01- 07-00-05-E00011 to A/LL.).
主 题：ADP P2Y13 ISG cAMP viral infection
摘 要：Among the most important sensors of extracellular danger signals, purinergic receptors have been demonstrated to play crucial roles in host defense against infection. However, the function of P2 receptors in viral infection has been little explored. Here we demonstrated that P2Y13 and its ligand ADP play an important role in protecting hosts from viral infections. First, we demonstrate that P2Y13, as a typical interferon-stimulated gene, is induced together with extracellular ADP during viral infection. Most importantly, extracellular ADP restricts the replication of different kinds of viruses, including vesicular stomatitis virus, Newcastle disease virus, herpes simplex virus 1, and murine leukemia virus. This kind of protection is dependent on P2Y13 but not P2Y1 or P2Y12, which are also considered as receptors for ADP. Furthermore, cyclic adenosine monophosphate and EPAC1 are downregu-lated by extracellular ADP through the P2Y13-coupled Gi alpha subunit. Accordingly, inhibition or deletion of EPAC1 significantly eliminates ADP/P2Y13-mediated antiviral activities. Taken together, our results show that P2Y13 and ADP play pivotal roles in the clearance of invaded virus and have the potential as antiviral targets.
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