Research
| Title： | The E3 ubiquitin ligase RNF182 regulates the induction of innate immune response against GCRV by mediating the ubiquitination of RIG-I in grass carp (Ctenopharyngodon idella) and rare minnow (Gobiocypris rarus) |
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| First author： | Lin, Yusheng; Feng, Haohao; Wang, Yuxuan; Liu, Shuai; Hu, Pengcheng; Wang, Jing; Cao, Hong |
| Journal： | FISH & SHELLFISH IMMUNOLOGY |
| Years： | 2025 |
| DOI： | 10.1016/j.fsi.2025.110244 |
| Abstract： | Innate immunity is the first line of antiviral or antimicrobial defence for the host. A cytoplasmic viral RNA sensor, which is known as retinoic acid-inducible gene 1 (RIG-I), makes a vital impact on the production of type I interferons (IFN) and eliminating RNA virus. This study indicated that E3 ubiquitin ligase RING finger protein 182 (RNF182) inhibited the antiviral activity of type I IFN in grass carp reovirus (GCRV)-infected cells by directly interplaying with RIG-I. The CiE3RNF182 cDNA encode a polypeptide of 158 amino acids. Cellular distribution analysis results suggested that cytoplasm was the main site of CiE3RNF182 location. Real-time quantitative PCR showed universal expression of CiE3RNF182 in all investigated tissues, with extremely high expression in liver. During virus infection, the CiE3RNF182 associates with the CiRIG-I and then induces the Lys-33-linked ubiquitin to the Lys33 residues of CiRIG-I to trigger its degradation, causing the inhibition of CiRIG-I downstream signalling. Furthermore, we obtained CRISPR/Cas9-mediated generation of E3RNF182-null rare minnows, finding that E3RNF182 deletion facilitates the survival ratio of GCRV-infected rare minnows. Additionally, the E3RNF182- /- rare minnows exhibited significantly lower relative copy number of GCRV compared to the wildtype group. In summary, our findings demonstrate the function of E3 ligase in controlling the anti-GCRV innate immunity through RIG-I in fish. |
