Hijacking of host negative regulator RIOK3 by a fish virus orchestrates stealthy subversion of interferon immunity
摘要
Viruses commonly evade host immunity by directly targeting and destroying positive regulators of interferon (IFN) signaling. Here, we reveal an indirect and stealthy immune evasion strategy employed by a fish virus, whereby the Spring Viraemia of Carp Virus (SVCV) phosphoprotein (P protein) antagonizes host IFN responses by upregulating the host negative regulator RIOK3. Proteomics analysis identified significant upregulation of the kinase RIOK3 upon SVCV infection. We demonstrate that fish RIOK3 negatively regulates type I IFN by recruiting the selective autophagy receptor p62 to mediate degradation of TBK1. Furthermore, the SVCV P protein stabilizes RIOK3 protein levels through the E3 ubiquitin ligase TRIM11. Functional assays confirmed that the inhibition of IFN by the P protein is enhanced by RIOK3 overexpression and significantly diminished upon RIOK3 knockdown. Our findings uncover a mechanism where SVCV P protein hijacks the host negative regulator RIOK3 to suppress IFN production indirectly, representing an efficient and stealthy viral immune evasion strategy.
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