White Spot Syndrome Virus Immediate-Early Protein (wsv100) Antagonizes the NF-kappaB Pathway to Inhibit Innate Immune Response in shrimp

Abstract

Viruses have evolved sophisticated strategies to evade host immune defenses, often targeting conserved signaling pathways. In shrimp, the NF-{kappa}B signaling pathway is crucial for antiviral immunity, yet its regulation during White Spot Syndrome Virus (WSSV) infection remains poorly understood. Here, we identify and characterize wsv100, an immediate-early (IE) protein of WSSV, as a key antagonist of the NF-{kappa}B pathway. wsv100 interacts directly with the transcription factor Dorsal and the adaptor protein IMD, preventing Dorsal phosphorylation by Pelle kinase. This inhibition suppresses Dorsals nuclear translocation and downstream expression of antimicrobial peptides (AMPs), essential for antiviral defense. Knockdown of wsv100 reduced WSSV replication, increased Dorsal phosphorylation, and enhanced AMP expression, leading to higher survival rates in infected shrimp. Conversely, wsv100 overexpression promoted WSSV replication and AMPs suppression. These findings reveal a novel immune evasion mechanism by which WSSV subverts the NF-{kappa}B pathway and highlight the evolutionary arms race between hosts and viruses. This study enhances our understanding of host-virus interactions and offers potential targets for antiviral strategies in shrimp aquaculture. Author SummaryThe innate immune system is the first line of defense against viral infections in invertebrates, with the NF-{kappa}B signaling pathway playing a central role in orchestrating antiviral responses. In this study, we uncover a novel immune evasion mechanism employed by White Spot Syndrome Virus (WSSV), a devastating pathogen in shrimp aquaculture. The WSSV immediate-early protein wsv100 directly targets the transcription factor Dorsal and prevents its phosphorylation by Pelle kinase, a critical step in NF-{kappa}B activation. This interaction suppresses Dorsals nuclear translocation and downstream expression of antimicrobial peptides (AMPs), thereby impairing the shrimps ability to mount an effective immune response. Knockdown of wsv100 significantly reduced WSSV replication and enhanced shrimp survival, while wsv100 overexpression had the opposite effect. These findings not only elucidate how WSSV exploits the NF-{kappa}B pathway but also underscore its central role in shrimp antiviral immunity. This work advances our understanding of host-virus co-evolution and provides a foundation for developing novel antiviral strategies to mitigate the economic losses caused by WSSV in shrimp aquaculture.