SAV Nsp2 regulates NF-κB signaling to induce inflammatory responses by targeting host DDX3. (March 2023)

• Record Type: Journal Article
• Authors: Gao, Shuai; Han, Bing; Xu, Baoxing; Wang, Na; Zhang, Yanru; Liu, Xuefei; Zhang, Mengmeng; Wang, Guanbo; Guan, Xueting; Huang, Jinshan; Liu, Min; Shi, Wen
• Is Part Of: Developmental and comparative immunology. Volume 140(2023)
• Publication Date: 2023-03
• Subjects: SAV -- Nsp2 -- DDX3 -- NF-κB -- Inflammatory responses; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2022.104612
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: Salmon alphavirus (SAV) infection leads to severe pancreas disease (PD) with typical inflammatory responses in Atlantic salmon ( Salmo salar ) and rainbow trout ( Oncorhynchus mykiss ). Nsp2, an important nonstructural protein of SAV, can activate NF-κB signaling pathway to reduce inflammatory responses. However, the molecular mechanism remains unclear. In this study, the ML (279-421aa) of Nsp2 was revealed to be the key domain for activating NF-κB. We focused on a host protein, DEAD-box RNA helicase 3 (DDX3), that may interact with Nsp2 to regulate NF-κB-induced inflammatory. The interaction between DDX3 and Nsp2 was confirmed in vitro . Overexpression of DDX3 inhibited the activation of NF-κB by Nsp2. SAV Nsp2 relieves the inhibitory effect of DDX3 on NF-κB, thereby initiating the innate immune response. This study revealed the molecular mechanism of Nsp2-induced inflammatory response by targeting DDX3 to activate NF-κB, providing a theoretical basis for revealing the underlying infection mechanism and pathogenesis of SAV. Highlights: ML (279-421aa) of SAV Nsp2 is the key domain for activating NF-κB to induce inflammatory responses. DDX3 negatively regulates Nsp2-activated NF-κB signaling pathway. SAV Nsp2 activates NF-κB to induce inflammatory response by targeting DDX3.