气候变化领域集成服务门户(CCPortal): Rotavirus induces intercellular calcium waves through ADP signaling

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DOI	10.1126/science.abc3621
	Rotavirus induces intercellular calcium waves through ADP signaling
	Chang-Graham A.L.; Perry J.L.; Engevik M.A.; Engevik K.A.; Scribano F.J.; Gebert J.T.; Danhof H.A.; Nelson J.C.; Kellen J.S.; Strtak A.C.; Sastri N.P.; Estes M.K.; Britton R.A.; Versalovic J.; Hyser J.M.
发表日期	2020
ISSN	0036-8075
卷号	370 期号:6519
英文摘要	Rotavirus causes severe diarrheal disease in children by broadly dysregulating intestinal homeostasis. However, the underlying mechanism(s) of rotavirus-induced dysregulation remains unclear. We found that rotavirus-infected cells produce paracrine signals that manifested as intercellular calcium waves (ICWs), observed in cell lines and human intestinal enteroids. Rotavirus ICWs were caused by the release of extracellular adenosine 5'-diphosphate (ADP) that activated P2Y1 purinergic receptors on neighboring cells. ICWs were blocked by P2Y1 antagonists or CRISPR-Cas9 knockout of the P2Y1 receptor. Blocking the ADP signal reduced rotavirus replication, inhibited rotavirus-induced serotonin release and fluid secretion, and reduced diarrhea severity in neonatal mice. Thus, rotavirus exploited paracrine purinergic signaling to generate ICWs that amplified the dysregulation of host cells and altered gastrointestinal physiology to cause diarrhea. © 2020 American Association for the Advancement of Science. All rights reserved.
英文关键词	adenosine diphosphate; calcium ion; cyclooxygenase 2; inducible nitric oxide synthase; interleukin 1alpha; purinergic P2 receptor antagonist; purinergic P2Y1 receptor; serotonin; adenosine diphosphate; calcium; purinergic P2Y receptor antagonist; purinergic P2Y1 receptor; gene expression; genetic engineering; medicine; physiology; rodent; signaling; virus; animal cell; animal experiment; animal model; Article; calcium signaling; cell line; controlled study; CRISPR-CAS9 system; disease severity; female; gene knockdown; host cell; human; human cell; human tissue; image analysis; immunoblotting; immunofluorescence; intercellular calcium wave; intestinal organoid; MA104-GECI cell line; male; microscopy; mouse; newborn; nonhuman; paracrine signaling; priority journal; protein expression; purinergic signaling; reverse transcription polymerase chain reaction; RNA extraction; Rotavirus; secretion (process); serotonin release; virus replication; animal; C57BL mouse; calcium signaling; drug effect; genetics; HEK293 cell line; jejunum; knockout mouse; metabolism; paracrine signaling; physiology; Rotavirus; Rotavirus infection; virology; Rotavirus; Adenosine Diphosphate; Animals; Calcium; Calcium Signaling; Female; HEK293 Cells; Humans; Jejunum; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Paracrine Communication; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y1; Rotavirus; Rotavirus Infections
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/243269
作者单位	Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States; Alkek Center for Metagenomic and Microbiome Research, Baylor College of Medicine, Houston, TX, United States; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States; Department of Pathology, Texas Children's Hospital, Houston, TX, United States; Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, United States
推荐引用方式 GB/T 7714	Chang-Graham A.L.,Perry J.L.,Engevik M.A.,et al. Rotavirus induces intercellular calcium waves through ADP signaling[J],2020,370(6519).
APA	Chang-Graham A.L..,Perry J.L..,Engevik M.A..,Engevik K.A..,Scribano F.J..,...&Hyser J.M..(2020).Rotavirus induces intercellular calcium waves through ADP signaling.Science,370(6519).
MLA	Chang-Graham A.L.,et al."Rotavirus induces intercellular calcium waves through ADP signaling".Science 370.6519(2020).