2. Academic Validation
  3. The Transient Receptor Potential Vanilloid 2 (TRPV2) Channel Facilitates Virus Infection Through the Ca2+ -LRMDA Axis in Myeloid Cells

The Transient Receptor Potential Vanilloid 2 (TRPV2) Channel Facilitates Virus Infection Through the Ca2+ -LRMDA Axis in Myeloid Cells

  • Adv Sci (Weinh). 2022 Oct 19;e2202857. doi: 10.1002/advs.202202857.
Yu-Yao Guo 1 2 3 4,  Yue Gao 1 4,  Yu-Ru Hu 5,  Yuhan Zhao 4,  Dexiang Jiang 4,  Yulin Wang 4,  Youjing Zhang 4,  Hu Gan 1 2 3,  Chang Xie 4,  Zheng Liu 5,  Bo Zhong 1 2 3,  Zhi-Dong Zhang 1 2 3,  Jing Yao 1 2 4
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, College of Life Sciences, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.
  • 2 Department of Immunology, Medical Research Institute and Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430071, China.
  • 3 Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, 430071, China.
  • 4 State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430072, China.
  • 5 The Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China.
PMID: 36261399 DOI: 10.1002/advs.202202857
Abstract

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;Trpv2fl/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 Trpv2fl/fl but not LyZ2-Cre;Trpv2fl/fl BMDCs. Consistently, complement of LRMDA into LyZ2-Cre;Trpv2fl/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.

Keywords

Ca2+ influx; Lrmda; TRPV2; antiviral immunity; myeloid cells; virus penetration.

Figures
Products