Fish SCD1 promotes SGIV infection via modulating the formation of lipid droplets and TBK1/MDA5-activated IFN signal pathway

Abstract

Stearoyl CoA desaturase (SCD1), the rate-limiting enzyme for monounsaturated fatty acid production, involved in host metabolic regulation. Recent reports indicated that SCD1 played a crucial role in the process of viral infection. To investigate the function of SCD1 in teleost fish and the role it played in fish virus infection, EcSCD1 was cloned and characterized in the orange-spotted grouper, Epinephelus coioides. The open reading frame (ORF) of EcSCD1 consisted of 1005 nucleotides encoding a protein containing 334 amino acids with a predicted molecular weight of 38.33 kDa, which shared 74.05% and 60.48% identity with zebrafish and human, respectively. EcSCD1 possessed four transmembrane domains and three conserved His-rich regions. In healthy groupers, EcSCD1 was primarily expressed in the liver and brain. Subcellular localization assay revealed that EcSCD1 was mainly distributed in the cytoplasm with uniform distribution or dot-like aggregation forms, and EcSCD1 was co-localized with the endoplasmic reticulum (ER). Singapore grouper iridovirus (SGIV) as well as poly (dA: dT) stimulation induced the expression of EcSCD1. On the other hand, EcSCD1 overexpression increased SGIV infection and SCD1 enzymatic product oleic acid (OA) recovered SGIV infection suppressed by SCD1 inhibitor. In addition, EcSCD1 overexpression facilitated the formation of lipid droplets (LDs), which was crucial for SGIV replication. Furthermore, EcSCD1 overexpression down-regulated the expression of interferon signaling molecules and the activities of interferon (IFN)1/3 and interferon stimulated response element (ISRE) promotors. Moreover, EcSCD1 overexpression restricted TANK binding kinase 1 (TBK1)−/melanoma differentiation-associated protein 5 (MDA5)-, but not mitochondrial antiviral signaling protein (MAVS)-evoked interferon immune responses. Overall, our findings offered novel insights into the regulatory mechanism of EcSCD1 during virus infection.