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研究揭示轮状病毒导致腹泻机制
作者:小柯机器人 发布时间:2020/11/22 1:29:41

美国贝勒医学院Joseph M. Hyser研究组取得最新进展。他们发现轮状病毒通过腺苷5'-二磷酸(ADP)信号传导诱导细胞间钙波(ICWs)。2020年11月20日出版的《科学》杂志发表了这项成果。

他们发现,轮状病毒感染的细胞产生旁分泌信号,表现为ICW,在细胞系和人小肠中观察到。轮状病毒ICW是由激活邻近细胞上的P2Y1嘌呤能受体的胞外ADP释放引起的。ICW被P2Y1拮抗剂或P2Y1受体的CRISPR-Cas9敲除所阻断。 阻断ADP信号可减少轮状病毒的复制,抑制轮状病毒诱导的5-羟色胺释放和体液分泌,并降低新生小鼠的腹泻严重程度。 因此,轮状病毒利用旁分泌嘌呤能信号转导产生ICW,从而放大宿主细胞的失调并改变胃肠道生理从而引起腹泻。

研究人员表示,轮状病毒通过广泛地调节肠道稳态而导致儿童严重的腹泻病。 然而,轮状病毒诱导失调的潜在机制仍不清楚。

附:英文原文

Title: Rotavirus induces intercellular calcium waves through ADP signaling

Author: Alexandra L. Chang-Graham, Jacob L. Perry, Melinda A. Engevik, Kristen A. Engevik, Francesca J. Scribano, J. Thomas Gebert, Heather A. Danhof, Joel C. Nelson, Joseph S. Kellen, Alicia C. Strtak, Narayan P. Sastri, Mary K. Estes, Robert A. Britton, James Versalovic, Joseph M. Hyser

Issue&Volume: 2020/11/20

Abstract: 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.

DOI: 10.1126/science.abc3621

Source: https://science.sciencemag.org/content/370/6519/eabc3621

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037