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| Main Authors: | , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Journal of immunology (Baltimore, Md. : 1950)
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40359380/ |
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| _version_ | 1868266204017197057 |
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| author | Huang, Wenji Wang, Yafang Ji, Ning Xiao, Hehe Chen, Kangyong Guo, Jiahong Feng, Jianhua Mustafa, Nageen Wang, Junya Feng, Hao Zou, Jun |
| author_facet | Huang, Wenji Wang, Yafang Ji, Ning Xiao, Hehe Chen, Kangyong Guo, Jiahong Feng, Jianhua Mustafa, Nageen Wang, Junya Feng, Hao Zou, Jun Huang, Wenji Wang, Yafang Ji, Ning Xiao, Hehe Chen, Kangyong Guo, Jiahong Feng, Jianhua Mustafa, Nageen Wang, Junya Feng, Hao Zou, Jun |
| collection | PubMed - marine biology |
| contents | Zebrafish TRIM2a promotes virus replication via ubiquitination of IRF3 and autophagic cargo receptor p62. Huang, Wenji Wang, Yafang Ji, Ning Xiao, Hehe Chen, Kangyong Guo, Jiahong Feng, Jianhua Mustafa, Nageen Wang, Junya Feng, Hao Zou, Jun Animals Zebrafish Ubiquitination Virus Replication Zebrafish Proteins Humans Interferon Regulatory Factor-3 HEK293 Cells Rhabdoviridae Tripartite Motif Proteins Autophagy Rhabdoviridae Infections Ubiquitin-Protein Ligases Interferons Fish Diseases A balanced IFN response, tightly regulated at multiple levels, is essential for host defense against viral infection. Tripartite motif-containing (TRIM) proteins are a large group of E3 ubiquitin ligases, and have been shown to be involved in the regulation of IFN response. However, the regulatory functions of individual TRIM proteins remain controversial. Here, we show that a virus-inducible TRIM2 homolog acts as a negative regulator for IFN production in zebrafish. Zebrafish Trim2a was upregulated in response to spring viremia of carp virus (SVCV) infection, and knockout of Trim2a significantly increased the expression of antiviral genes, leading to enhanced resistance to SVCV. Overexpression of Trim2a resulted in pronounced ubiquitination of IFN regulatory factor 3 (IRF3) via K11, K27, K29, and K48, promoting IRF3 degradation and stability of SVCV phosphoprotein to favor viral replication. Moreover, TRIM2a induced ubiquitination of autophagic cargo receptor p62, which then interacted with IRF3, instigating IRF3 degradation. Further, the inhibitory effects of TRIM2a on IFN production were also observed in human HEK293 cells, suggesting that the regulatory functions of TRIM2 are likely to be conserved during evolution. Collectively, our findings demonstrate that TRIM2a is a negative regulator of IFN production, and could serve as a potential target to dampen exacerbated IFN response triggered by aberrant activation of retinoic acid-inducible gene 1 (RIG-I)-like receptors. Our study provides insights into a previously uncharacterized role of TRIM2 in the regulation of IFN signaling. |
| format | Artículo científico |
| id | pubmed_40359380 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Journal of immunology (Baltimore, Md. : 1950) |
| record_format | pubmed |
| spellingShingle | Zebrafish TRIM2a promotes virus replication via ubiquitination of IRF3 and autophagic cargo receptor p62. Huang, Wenji Wang, Yafang Ji, Ning Xiao, Hehe Chen, Kangyong Guo, Jiahong Feng, Jianhua Mustafa, Nageen Wang, Junya Feng, Hao Zou, Jun Animals Zebrafish Ubiquitination Virus Replication Zebrafish Proteins Humans Interferon Regulatory Factor-3 HEK293 Cells Rhabdoviridae Tripartite Motif Proteins Autophagy Rhabdoviridae Infections Ubiquitin-Protein Ligases Interferons Fish Diseases Zebrafish TRIM2a promotes virus replication via ubiquitination of IRF3 and autophagic cargo receptor p62. Huang, Wenji Wang, Yafang Ji, Ning Xiao, Hehe Chen, Kangyong Guo, Jiahong Feng, Jianhua Mustafa, Nageen Wang, Junya Feng, Hao Zou, Jun Animals Zebrafish Ubiquitination Virus Replication Zebrafish Proteins Humans Interferon Regulatory Factor-3 HEK293 Cells Rhabdoviridae Tripartite Motif Proteins Autophagy Rhabdoviridae Infections Ubiquitin-Protein Ligases Interferons Fish Diseases A balanced IFN response, tightly regulated at multiple levels, is essential for host defense against viral infection. Tripartite motif-containing (TRIM) proteins are a large group of E3 ubiquitin ligases, and have been shown to be involved in the regulation of IFN response. However, the regulatory functions of individual TRIM proteins remain controversial. Here, we show that a virus-inducible TRIM2 homolog acts as a negative regulator for IFN production in zebrafish. Zebrafish Trim2a was upregulated in response to spring viremia of carp virus (SVCV) infection, and knockout of Trim2a significantly increased the expression of antiviral genes, leading to enhanced resistance to SVCV. Overexpression of Trim2a resulted in pronounced ubiquitination of IFN regulatory factor 3 (IRF3) via K11, K27, K29, and K48, promoting IRF3 degradation and stability of SVCV phosphoprotein to favor viral replication. Moreover, TRIM2a induced ubiquitination of autophagic cargo receptor p62, which then interacted with IRF3, instigating IRF3 degradation. Further, the inhibitory effects of TRIM2a on IFN production were also observed in human HEK293 cells, suggesting that the regulatory functions of TRIM2 are likely to be conserved during evolution. Collectively, our findings demonstrate that TRIM2a is a negative regulator of IFN production, and could serve as a potential target to dampen exacerbated IFN response triggered by aberrant activation of retinoic acid-inducible gene 1 (RIG-I)-like receptors. Our study provides insights into a previously uncharacterized role of TRIM2 in the regulation of IFN signaling. |
| title | Zebrafish TRIM2a promotes virus replication via ubiquitination of IRF3 and autophagic cargo receptor p62. |
| topic | Animals Zebrafish Ubiquitination Virus Replication Zebrafish Proteins Humans Interferon Regulatory Factor-3 HEK293 Cells Rhabdoviridae Tripartite Motif Proteins Autophagy Rhabdoviridae Infections Ubiquitin-Protein Ligases Interferons Fish Diseases |
| url | https://pubmed.ncbi.nlm.nih.gov/40359380/ |