CqSESN2 suppresses WSSV infection via the CqNrf2 antioxidant pathway in Cherax quadricarinatus.

Abstract

White spot syndrome virus (WSSV) is a devastating pathogen causing substantial economic losses in crustacean aquaculture. Successful viral replication depends on complex interactions with host cellular processes, including those that maintain redox homeostasis. However, the molecular mechanisms by which host antioxidant proteins influence WSSV replication remain poorly understood. In this study, we characterized a sestrin 2 homolog, CqSESN2, from red claw crayfish (Cherax quadricarinatus) and investigated its role in WSSV infection. The full-length cDNA of CqSESN2 contained an open reading frame of 1,242 bp encoding 413 amino acids. Phylogenetic analysis revealed that CqSESN2 is a conserved SESN2 family member. CqSESN2 was ubiquitously expressed in all examined tissues and significantly upregulated upon WSSV infection. Knockdown of CqSESN2 significantly enhanced WSSV replication, indicating an antiviral role for CqSESN2. Mechanistically, CqSESN2 functioned as a conserved negative regulator of intracellular reactive oxygen species (ROS), as its silencing led to elevated ROS levels. ROS scavenger NAC abolished WSSV-induced CqSESN2 upregulation, confirming ROS-dependent expression. Furthermore, CqSESN2 activated the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant pathway, promoting downstream antioxidant genes (CqGST, CqSrx, CqHO-1) and its own expression, forming a positive feedback loop. Pulldown assays revealed a specific interaction between CqSESN2 and Cqp62. Simultaneous knockdown of both CqSESN2 and CqNrf2 synergistically enhanced viral replication. Collectively, these findings reveal that CqSESN2 is an antiviral protein that inhibits WSSV replication by modulating ROS homeostasis and activating the Nrf2-mediated antioxidant response, providing new insights into host-virus interactions in crustaceans and potential targets for antiviral strategies in aquaculture.

Key Findings

• CqSESN2 is a conserved sestrin 2 homolog in Cherax quadricarinatus that is upregulated upon WSSV infection.
• Knockdown of CqSESN2 increases WSSV replication and intracellular ROS levels, indicating its antiviral role via ROS regulation.
• CqSESN2 activates the Nrf2-mediated antioxidant pathway, promoting antioxidant gene expression and forming a positive feedback loop to suppress viral replication.

Clinical Significance

Citation

Wang Yan, Cai Kai-Ming, Zeng Xuanet al.. CqSESN2 suppresses WSSV infection via the CqNrf2 antioxidant pathway in Cherax quadricarinatus. Fish & shellfish immunology. 2026-Aug-21.