2. Academic Validation
  3. Viral infection and spread are inhibited by the polyubiquitination and downregulation of TRPV2 channel by the interferon-stimulated gene TRIM21

Viral infection and spread are inhibited by the polyubiquitination and downregulation of TRPV2 channel by the interferon-stimulated gene TRIM21

  • Cell Rep. 2024 Apr 23;43(4):114095. doi: 10.1016/j.celrep.2024.114095.
Yu-Yao Guo 1,  Yue Gao 2,  Yun-Lin Zhao 2,  Chang Xie 2,  Hu Gan 2,  Xufeng Cheng 2,  Li-Ping Yang 3,  Junyan Hu 2,  Hong-Bing Shu 1,  Bo Zhong 4,  Dandan Lin 5,  Jing Yao 6
Affiliations

Affiliations

  • 1 Cancer Center, Renmin Hospital of Wuhan University, State Key Laboratory of Virology, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430072, Hubei, China; Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430072, Hubei, China.
  • 2 Cancer Center, Renmin Hospital of Wuhan University, State Key Laboratory of Virology, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430072, Hubei, China.
  • 3 Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430072, Hubei, China.
  • 4 Cancer Center, Renmin Hospital of Wuhan University, State Key Laboratory of Virology, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430072, Hubei, China; Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430072, Hubei, China; Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan 430072, Hubei, China. Electronic address: zhongbo@whu.edu.cn.
  • 5 Cancer Center, Renmin Hospital of Wuhan University, State Key Laboratory of Virology, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430072, Hubei, China. Electronic address: lindandan@whu.edu.cn.
  • 6 Cancer Center, Renmin Hospital of Wuhan University, State Key Laboratory of Virology, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430072, Hubei, China; Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan 430072, Hubei, China. Electronic address: jyao@whu.edu.cn.
PMID: 38613787 DOI: 10.1016/j.celrep.2024.114095
Abstract

Interferon (IFN) contributes to the host's Antiviral response by inducing IFN-stimulated genes (ISGs). However, their functional targets and the mechanism of action remain elusive. Here, we report that one such ISG, TRIM21, interacts with and degrades the TRPV2 channel in myeloid cells, reducing its expression and providing host protection against viral infections. Moreover, viral Infection upregulates TRIM21 in paracrine and autocrine manners, downregulating TRPV2 in neighboring cells to prevent viral spread to uninfected cells. Consistently, the Trim21-/- mice are more susceptible to HSV-1 and VSV Infection than the Trim21+/+ littermates, in which viral susceptibility is rescued by inhibition or deletion of TRPV2. Mechanistically, TRIM21 catalyzes the K48-linked ubiquitination of TRPV2 at Lys295. TRPV2K295R is resistant to viral-infection-induced TRIM21-dependent ubiquitination and degradation, promoting viral Infection more profoundly than wild-type TRPV2 when reconstituted into Lyz2-Cre;Trpv2fl/fl myeloid cells. These findings characterize targeting the TRIM21-TRPV2 axis as a conducive strategy to control viral spread to bystander cells.

Keywords

CP: Immunology; CP: Microbiology; Ca(2+) signal; TRIM21; TRPV2; interferon-stimulated gene; plasma membrane tension; ubiquitination; viral penetration.

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