Proteasome subunit beta type-8 from sevenband grouper negatively regulates cytokine responses by interfering NF-κB signaling upon nervous necrosis viral infection.

During viral infection, proper regulation of immune signaling is essential to ensure successful clearance of virus. Immunoproteasome is constitutively expressed and gets induced during viral infection by interferon signaling and contributes to regulate proinflammatory cytokine production and activation of the NF-κB pathway. In this study, we identified Hs-PSMB8, a member of the proteasome β-subunits (PSMB) family, as a negative regulator of NF-κB responses during NNV infection. The transient expression of Hs-PSMB8 delayed the appearance of cytopathic effect (CPE) and showed a higher viral load. The Hs-PSMB8 interacted with NNV which was confirmed using immunocolocalization and co-IP. Overexpression of Hs-PSMB8 diminished virus induced activation of the NF-κB promoters and downregulated the activation of IL-1β, TNFα, IL6, IL8, IFNγ expression upon NNV infection. Collectively, our results demonstrate that PSMB8 is an important regulator of NF-κB signaling during NNV infection in sevenband grouper. • NNV infection induced transcriptional upregulation of Hs-PSMB8 in sevenband grouper tissues. • The transient expression of Hs-PSMB8 delayed the appearance of cytopathic effect and showed a higher NNV load. • The Hs-PSMB8 interacted with NNV and diminishes virus induced activation of NF-κB responses. • The Hs-PSMB8 downregulated the activation IL-1β, TNFα, IL6, IL8, IFNγ expression upon NNV infection. [ABSTRACT FROM AUTHOR]