title: Investigating the antiviral role of cell death-inducing DFF45-like effector B in HCV replication.
abstract: Cell-death-inducing DFF45-like effector B (CIDEB) is an apoptotic host factor, which was recently found to also regulate hepatic lipid homeostasis. Herein we delineate the relevance of these dual roles of CIDEB in apoptosis and lipid metabolism in the context of hepatitis C virus (HCV) replication. We demonstrate that HCV upregulates CIDEB expression in human serum differentiated hepatoma cells. CIDEB overexpression inhibits HCV replication in HCV replicon expressing Huh7.5 cells, while small interfering RNA knockdown of CIDEB expression in human serum differentiated hepatoma cells promotes HCV replication and secretion of viral proteins. Furthermore, we characterize a CIDEB mutant, KRRA, which is deficient in lipid droplet clustering and fusion and demonstrate that CIDEB-mediated inhibition of HCV is independent of the protein's lipid droplet fusogenic role. Our results suggest that higher levels of CIDEB expression, which favour an apoptotic role for the host factor, inhibit HCV. Collectively, our data demonstrate that CIDEB can act as an anti-HCV host factor and contribute to altered triglyceride homeostasis.
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada; National Research Council of Canada, Ottawa, Ontario, Canada.
authors: Ragunath
authors: R
authors: Singaravelu
authors: Julie
authors: J
authors: Delcorde
authors: Rodney K
authors: RK
authors: Lyn
authors: Rineke H
authors: RH
authors: Steenbergen
authors: Daniel M
authors: DM
authors: Jones
authors: David Lorne
authors: DL
authors: Tyrrell
authors: Rodney S
authors: RS
authors: Russell
authors: John P
authors: JP
authors: Pezacki
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D006706:Homeostasis; D054884:Host-Pathogen Interactions; D006801:Humans; D050356:Lipid Metabolism; D014280:Triglycerides / Q000378:metabolism; D014779:Virus Replication
chemical_list: D051017:Apoptosis Regulatory Proteins; C112511:CIDEB protein, human; D014280:Triglycerides; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases
keywords: CARS microscopy; apoptosis; cell-inducing DFF45 like effector; hepatitis C virus; lipid droplet