The Transient Receptor Potential Vanilloid 2 (TRPV2) Channel Facilitates Virus Infection Through the Ca(2+) -LRMDA Axis in Myeloid Cells.
The Transient Receptor Potential Vanilloid 2 (TRPV2) Channel Facilitates Virus Infection Through the Ca(2+) -LRMDA Axis in Myeloid Cells.
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瞬时受体电位 Vanilloid 2 (TRPV2) 通道通过骨髓细胞中的 Ca 2 –LRMDA 轴促进病毒感染
DOI：
10.1002/advs.202202857
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发表时间：
2022-12
期刊：
影响因子：
15.1
通讯作者：
Yao, Jing
中科院分区：
文献类型：
--
作者：
Guo, Yu-Yao;Gao, Yue;Hu, Yu-Ru;Zhao, Yuhan;Jiang, Dexiang;Wang, Yulin;Zhang, Youjing;Gan, Hu;Xie, Chang;Liu, Zheng;Zhong, Bo;Zhang, Zhi-Dong;Yao, Jing
瞬时受体电位香草蛋白2 （TRPV2）通道是一种非选择性阳离子通道，参与神经系统的多种感觉过程。研究表明，髓细胞中的TRPV2通过Ca2+ - LRMDA轴促进细胞膜的张力和流动性，从而促进病毒渗透。敲除骨髓细胞中的TRPV2或抑制TRPV2通道活性可抑制病毒感染并保护小鼠免受单纯疱疹病毒1 （HSV‐1）和水疱性口炎病毒（VSV）感染。在LyZ2‐Cre中重组TRPV2而不是Ca2+不渗透突变体TRPV2E572Q；Trpv2 fl/fl骨髓源性树突状细胞（bmdc）恢复病毒感染。从机制上讲，敲除骨髓细胞中的TRPV2可抑制细胞膜的张力和流动性以及病毒的渗透，这可以通过TRPV2的重构而不是TRPV2E572Q来恢复。此外，敲除TRPV2导致BMDCs和BMDMs中Lrmda的下调，Lrmda的敲除显著下调细胞膜的流动性和张力，抑制TRPV2 fl/fl的病毒感染，但对LyZ2‐Cre没有抑制作用；Trpv2 fl/fl bmdc。一致地，LRMDA补体进入LyZ2‐Cre；Trpv2 fl/fl BMDCs部分恢复细胞膜张力和流动性，促进病毒渗透和感染。这些发现表征了骨髓TRPV2通过Ca2+‐LRMDA轴促进病毒感染的先前未知功能。瞬时受体电位香草蛋白2 （TRPV2）通道是广泛分布于神经和非神经系统的多模态离子通道。研究表明，TRPV2通过维持依赖于Ca2+ - LRMDA轴的细胞膜张力和流动性，促进病毒进入髓细胞。这些发现强调了TRPV2在髓细胞病毒感染中的重要作用。
The transient receptor potential vanilloid 2 (TRPV2) channel is a nonselective cation channel that has been implicated in multiple sensory processes in the nervous system. Here, it is shown that TRPV2 in myeloid cells facilitates virus penetration by promoting the tension and mobility of cell membrane through the Ca2+‐LRMDA axis. Knockout of TRPV2 in myeloid cells or inhibition of TRPV2 channel activity suppresses viral infection and protects mice from herpes simplex virus 1 (HSV‐1) and vesicular stomatitis virus (VSV) infection. Reconstitution of TRPV2 but not the Ca2+‐impermeable mutant TRPV2E572Q into LyZ2‐Cre;Trpv2 fl/fl bone marrow‐derived dendritic cells (BMDCs) restores viral infection. Mechanistically, knockout of TRPV2 in myeloid cells inhibits the tension and mobility of cell membrane and the penetration of viruses, which is restored by reconstitution of TRPV2 but not TRPV2E572Q. In addition, knockout of TRPV2 leads to downregulation of Lrmda in BMDCs and BMDMs, and knockdown of Lrmda significantly downregulates the mobility and tension of cell membrane and inhibits viral infections in Trpv2 fl/fl but not LyZ2‐Cre;Trpv2 fl/fl BMDCs. Consistently, complement of LRMDA into LyZ2‐Cre;Trpv2 fl/fl BMDCs partially restores the tension and mobility of cell membrane and promotes viral penetration and infection. These findings characterize a previously unknown function of myeloid TRPV2 in facilitating viral infection though the Ca2+‐LRMDA axis. The transient receptor potential vanilloid 2 (TRPV2) channel is a multimodal ion channel widely distributed in nervous and non‐nervous system. Here, it is shown that TRPV2 facilitates viral entry in myeloid cells via maintaining the tensile force and mobility of cell membrane dependently on the Ca2+‐LRMDA axis. These findings highlight essential roles of TRPV2 in viral infection in myeloid cells.
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