Key Points
CP potentiates RGNNV proliferation by suppressing the RLR-IFN signaling pathway.
CP promotes LjRNF114-mediated K48 ubiquitination and degradation of LjTRAF3.
CP promotes the K48-linked ubiquitination and degradation of LjIRF3.
Abstract
Nervous necrosis virus (NNV), a highly pathogenic RNA virus, is a major pathogen in the global aquaculture industry. To efficiently infect fish, NNV must evade or subvert the host IFN for their replication; however, the precise mechanisms remain to be elucidated. In this study, we reported that capsid protein (CP) of red-spotted grouper NNV (RGNNV) suppressed the IFN antiviral response to promote RGNNV replication in Lateolabrax japonicus brain cells, which depended on the ARM, S, and P domains of CP. CP showed an indirect or direct association with the key components of retinoic acid–inducible gene-I–like receptors signaling, L. japonicus TNFR-associated factor 3 (LjTRAF3) and IFN regulatory factor (LjIRF3), respectively, and degraded LjTRAF3 and LjIRF3 through the ubiquitin-proteasome pathway in HEK293T cells. Furthermore, we found that CP potentiated LjTRAF3 K48 ubiquitination degradation in a L. japonicus ring finger protein 114–dependent manner. LjIRF3 interacted with CP through the S domain of CP and the transcriptional activation domain or regulatory domain of LjIRF3. CP promoted LjIRF3 K48 ubiquitination degradation, leading to the reduced phosphorylation level and nuclear translocation of LjIRF3. Taken together, we demonstrated that CP inhibited type I IFN response by a dual strategy to potentiate the ubiquitination degradation of LjTRAF3 and LjIRF3. This study reveals a novel mechanism of RGNNV evading host immune response via its CP protein that will provide insights into the complex pathogenesis of NNV.
Footnotes
This work was supported by the National Natural Science Foundation of China (NSF), the Foundation for Innovative Research Groups of the NSF (32173001); the Bureau of Science and Information Technology of Guangzhou Municipality (Pearl River S&T Nova Program of Guangzhou) (201806010047); the China Postdoctoral Science Foundation–Funded Project (2019M653152); the Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation) (2019A1515110842); and the Natural Science Foundation of Guangxi Province (Guangxi Natural Science Foundation) (2021GXNSFDA075015).
The online version of this article contains supplemental material.
- Received July 13, 2021.
- Accepted January 10, 2022.
- Copyright © 2022 by The American Association of Immunologists, Inc.
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