Abstract
Considerable attention has been paid to the roles of lipid metabolism in virus infection due to its regulatory effects on virus replication and host antiviral immune response. However, few literature has focused on whether lipid metabolism is involved in the life cycle of lower vertebrate viruses. Singapore grouper iridovirus (SGIV) is the causative aquatic virus that extensively causes fry and adult groupers death. Here, the potential roles of cellular de novo fatty acid synthesis in SGIV infection was investigated. SGIV infection not only increased the expression levels of key enzymes in fatty acid synthesis in vivo/vitro, including acetyl-Coenzyme A carboxylase alpha (ACC1), fatty acid synthase (FASN), medium-chain acyl-CoA dehydrogenase (MCAD), adipose triglyceride lipase (ATGL), lipoprotein lipase (LPL) and sterol regulatory element-binding protein-1 (SREBP1), but it also induced the formation of lipid droplets (LDs), suggesting that SGIV altered de novo fatty acid synthesis in host cells. Using the inhibitor and specific siRNA of ACC1 and FASN, we found that fatty acid synthesis was essential for SGIV replication, evidenced by their inhibitory effects on CPE progression, viral gene transcription, protein expression and virus production. Moreover, the inhibitor of fatty acid β-oxidation could also reduce SGIV replication. Inhibition of fatty acid synthesis but not β-oxidation markedly blocked virus entry during the life cycle of SGIV infection. In addition, we also found that inhibition of ACC1 and FASN increased the IFN immune and inflammatory response during SGIV infection. Together, our data demonstrated that SGIV infection in vitro regulated host lipid metabolism and, in that process, cellular fatty acid synthesis might exert crucial roles during SGIV infection via regulating virus entry and host immune response.
Highlights
Introduction published maps and institutional affilIncreased studies have indicated that many viruses could disrupt or rearrange host lipid metabolism, especially the core metabolic pathways, including the metabolism of triglyceride, phospholipid, and cholesterol, to facilitate their virus replication [1–3]
We first examined the transcription levels of key enzymes involved in fatty acid synthesis in Singapore grouper iridovirus (SGIV)-infected cells, including Acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), sterol regulatory element-binding protein-1 (SREBP1), adipose triglyceride lipase (ATGL), medium-chain acyl-CoA dehydrogenase (MCAD) and lipoprotein lipase (LPL)
To assess whether fatty acid synthesis is involved in SGIV replication, we focused on ACC1 and FASN, the two most crucial restriction enzymes, and explored their roles in SGIV infection by corresponding inhibitors and specific siRNA
Summary
Increased studies have indicated that many viruses could disrupt or rearrange host lipid metabolism, especially the core metabolic pathways, including the metabolism of triglyceride, phospholipid, and cholesterol, to facilitate their virus replication [1–3]. Human cytomegalovirus (HCMV) activates glycolysis to supply the tricarboxylic acid cycle during infection, eventually producing fatty acids that are important for infection. Herpesvirus, hepatitis B virus (HBV), Epstein–Barr virus (EBV), human immunodeficiency virus (HIV) and measles virus all disturb or induce fatty acid synthesis [2,4]. Hepatitis C virus (HCV) disrupts different facets of lipid metabolism, alters phospholipid metabolism, and terminates fatty acid transport in mitochondria. HCV virus regulates a key flux-controlling enzyme, cholesterol synthase HMGCR (3-Hydroxy-3-Methylglutaryl-CoA Reductase), to affect the distribution and abnormal iations
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