Viral infection and spread are inhibited by the polyubiquitination and downregulation of TRPV2 channel by the interferon-stimulated gene TRIM21
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Cell reports - 43(2024), 4 vom: 23. Apr., Seite 114095 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Yu-Yao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.04.2024 Date Revised 27.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2024.114095 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM37103096X |
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| 041 | |a eng | ||
| 100 | 1 | |a Guo, Yu-Yao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Viral infection and spread are inhibited by the polyubiquitination and downregulation of TRPV2 channel by the interferon-stimulated gene TRIM21 |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 26.04.2024 | ||
| 500 | |a Date Revised 27.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a CP: Microbiology | |
| 650 | 4 | |a Ca(2+) signal | |
| 650 | 4 | |a TRIM21 | |
| 650 | 4 | |a TRPV2 | |
| 650 | 4 | |a interferon-stimulated gene | |
| 650 | 4 | |a plasma membrane tension | |
| 650 | 4 | |a ubiquitination | |
| 650 | 4 | |a viral penetration | |
| 650 | 7 | |a SS-A antigen |2 NLM | |
| 650 | 7 | |a TRPV Cation Channels |2 NLM | |
| 650 | 7 | |a Ribonucleoproteins |2 NLM | |
| 650 | 7 | |a Interferons |2 NLM | |
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| 700 | 1 | |a Gao, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yun-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Gan, Hu |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Xufeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Li-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Junyan |e verfasserin |4 aut | |
| 700 | 1 | |a Shu, Hong-Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Dandan |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Jing |e verfasserin |4 aut | |
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