The E3 ligase RNF5 facilitates viral replication by suppressing innate immune responses in grouper

Area of Science:

• Aquatic animal health
• Fish immunology
• Viral pathogenesis

Background:

• Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV) cause significant losses in grouper aquaculture.
• The role of ring finger protein 5 (RNF5), an E3 ubiquitin ligase, in teleost antiviral immunity is not well understood.

Purpose of the Study:

• To identify and characterize the EcRNF5 gene from Epinephelus coioides.
• To investigate the function of EcRNF5 in antiviral innate immunity against SGIV and RGNNV.

Main Methods:

• Gene identification and sequence analysis of EcRNF5.
• Expression analysis in grouper spleen cells post-viral challenge.
• In vitro assays to assess viral replication and immune gene expression.
• Co-immunoprecipitation assays to determine protein interactions.

Main Results:

• EcRNF5 expression was upregulated upon SGIV and RGNNV infection.
• Overexpression of EcRNF5 promoted SGIV and RGNNV replication.
• EcRNF5 suppressed the expression of interferon-related genes and pro-inflammatory cytokines.
• EcRNF5 interacted with key innate immune signaling molecules (EcSTING, EcTBK1, EcIRF3, EcIRF7) and inhibited their signaling pathways.

Conclusions:

• EcRNF5 plays a crucial role in antagonizing antiviral immunity in grouper.
• The findings elucidate the molecular mechanisms of EcRNF5 in facilitating SGIV and RGNNV pathogenicity.
• This study provides insights into fish-virus interactions and potential targets for disease control.