The TNF-TNFR-TRAF6 axis mediates NF-κB-dependent antiviral immunity against DIV1 in shrimp

Tumor necrosis factor (TNF) and its receptor (TNFR) form a central signaling axis in vertebrate immunity, yet their roles in invertebrate antiviral defense remain poorly defined. Here, we identified a structurally complete tumor necrosis factor receptor (LvTNFR) in Litopenaeus vannamei and demonstrated its critical role, together with its ligand LvTNF, in antiviral defense against decapod iridescent virus 1 (DIV1). Phylogenetic analysis placed LvTNFR within the invertebrate TNFR clade, which lacks a DEATH domain but retains a conserved TNFR-associated factor (TRAF)-binding motif. Both LvTNF and LvTNFR were transcriptionally upregulated following DIV1 infection, and RNA interference-mediated silencing of either gene resulted in increased viral replication and reduced shrimp survival. Protein interaction assays confirmed that LvTNFR specifically associates with LvTRAF6, establishing a TNF-TNFR-TRAF6 signaling axis. Functional analysis showed that this axis activates the NF-κB homolog LvDorsal, promotes its nuclear translocation, and induces antimicrobial peptide expression. Transcriptome profiling further identified immune-related downstream effectors, including the PH domain leucine-rich repeat protein phosphatase (PHLPP), whose suppression may enhance nuclear factor kappa B (NF-κB) activation via the Akt-IKK pathway. Collectively, these findings uncover a conserved TNF-TNFR-TRAF6 axis in shrimp, providing mechanistic insight into invertebrate antiviral immunity and suggesting a potential genetic target for disease-resistant shrimp breeding.