下调和上调
泛素
干扰素
基因
病毒学
SAMHD1公司
细胞生物学
病毒复制
生物
化学
遗传学
病毒
核糖核酸
逆转录酶
作者
Yu‐Yao Guo,Yue Gao,Yunlin Zhao,Chang Xie,Hu Gan,Xinyi Cheng,Liping Yang,Junyan Hu,Hong‐Bing Shu,Bo Zhong,Dandan Lin,Jing Yao
出处
期刊:Cell Reports
[Elsevier]
日期:2024-04-01
卷期号:43 (4): 114095-114095
标识
DOI:10.1016/j.celrep.2024.114095
摘要
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.
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