TRIM22 in Litopenaeus vannamei activates Dorsal by accelerating Cactus's degradation to mediate antiviral immunity.

Abstract

Tripartite motif protein 22 (TRIM22), an interferon-inducible E3 ubiquitin ligase, mediates antiviral responses in mammals by regulating NF-κB signaling. However, its functional role in invertebrates remains unknown. This study characterizes a TRIM22 ortholog (LvTRIM22) in Pacific white shrimp (Litopenaeus vannamei) and elucidates its molecular mechanism against white spot syndrome virus (WSSV). Upon WSSV infection, LvTRIM22 was transcriptionally upregulated. Co-immunoprecipitation assays revealed that LvTRIM22 bound to LvCactus (an IκB homolog) and mediated its K48-linked polyubiquitination and proteasomal degradation. Dual-luciferase reporter assays demonstrated that LvTRIM22 activated the Toll4-Dorsal-AMPs axis, thereby inducing expression of LvALF1 and LvLYZ1, two antimicrobial peptides with potent anti-WSSV activity. Consistently, knockdown of LvTRIM22 suppressed LvALF1 and LvLYZ1 expression, elevated viral loads, and increased shrimp mortality. All in all, LvTRIM22 acts as a critical E3 ubiquitin ligase that degrades LvCactus to activate the Dorsal-AMPs axis, conferring antiviral immunity against WSSV. This work provides the first evidence of TRIM22-mediated NF-κB regulation in invertebrates and highlights its potential for molecular breeding of WSSV-resistant shrimp.