The crucial role of intercellular calcium wave propagation triggered by influenza A virus in promoting infection.

IF 8.2 2区 生物学 Q1 CELL BIOLOGY
Fumiya Kozawa, Tomokazu Tamura, Naoki Takahashi, Taishi Kakizuka, Taro Ichimura, Rumi Shimada, Yasuyuki Hashimoto, Hironoshin Onizuska, Sayaka Kashiwagi, Tomoko Kamasaki, Maho Amano, Takeharu Nagai, Takasuke Fukuhara, Yoichiro Fujioka, Yusuke Ohba
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引用次数: 0

Abstract

Background: Influenza A viruses (IAVs) initially infect a few host cells before spreading to neighboring cells. However, the molecular mechanisms underlying this dissemination remain unclear. We have previously demonstrated that intracellular Ca2+ plays a crucial role in facilitating IAV infection. This study aims to clarify the connections between intracellular Ca2+ dynamics and spread of IAV infection.

Methods: Madin-Darby canine kidney (MDCK) cells stably expressing a Ca2+ indicator for optical imaging were established. Cells were cultured in Matrigel to form monolayers, and cell-to-cell Ca2+ dynamics within IAV-infected cells were analyzed using fluorescence microscopy.

Results: IAV infection upregulated the frequency of intercellular calcium wave propagations (iCWPs), facilitating viral spread. ADP released from initially infected cells mediated iCWPs via the P2Y1 receptor. P2Y1 antagonist suppressed both the generation of iCWPs and spread of viral infection. Enhanced endocytosis by the surrounding cells that received ADP signaling upregulated viral entry. Expression of IAV matrix protein 2 (M2) in initially infected cells triggered iCWPs through ADP diffusion, thereby increasing infection. Conversely, an ion permeability-deficient mutation of M2 or inhibition of its ion channel activity suppressed iCWPs.

Conclusions: Intercellular calcium signaling plays a crucial role in the early expansion and establishment of IAV infection, presenting a potential target for IAV prophylaxis.

甲型流感病毒引发的细胞间钙波传播在促进感染中的关键作用。
背景:甲型流感病毒(IAVs)最初感染少数宿主细胞,然后扩散到邻近细胞。然而,这种传播的分子机制尚不清楚。我们之前已经证明细胞内Ca2+在促进IAV感染中起着至关重要的作用。本研究旨在阐明细胞内Ca2+动力学与IAV感染传播之间的联系。方法:建立稳定表达Ca2+指示物的犬肾(MDCK)细胞。细胞在Matrigel中培养形成单层,使用荧光显微镜分析iav感染细胞内细胞间Ca2+动力学。结果:IAV感染上调细胞间钙波传播(iCWPs)频率,促进病毒传播。最初感染细胞释放的ADP通过P2Y1受体介导iCWPs。P2Y1拮抗剂抑制iCWPs的产生和病毒感染的传播。接受ADP信号的周围细胞内吞作用增强,病毒进入上调。最初感染细胞中IAV基质蛋白2 (M2)的表达通过ADP扩散触发iCWPs,从而增加感染。相反,M2的离子渗透性缺陷突变或其离子通道活性的抑制抑制了iCWPs。结论:细胞间钙信号在IAV感染的早期扩展和建立中起着至关重要的作用,是预防IAV的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
11.00
自引率
0.00%
发文量
180
期刊介绍: Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.
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