Investigating the antiviral role of cell death-inducing DFF45-like effector B in HCV replication

Download
  1. Get@NRC: Investigating the antiviral role of cell death-inducing DFF45-like effector B in HCV replication (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1111/febs.12901
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleFEBS Journal
ISSN1742-464X
Volume281
Issue16
Pages37513765; # of pages: 15
Subjectcell death inducing DFF45 like effector b; host factor; small interfering RNA; unclassified drug; virus protein; apoptosis; controlled study; hepatitis C; lipid metabolism; nucleotide sequence; protein expression; protein function; protein secretion; replicon; upregulation; virus inhibition; virus replication; CARS microscopy; cell-inducing DFF45 like effector; lipid droplet; Apoptosis Regulatory Proteins; Caspase 3; Caspase 7; Caspases; Cell Line, Tumor; Hepacivirus; Homeostasis; Host-Pathogen Interactions; Lipid Metabolism; Triglycerides
AbstractCell-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. Here, we illustrate that hepatitis C virus (HCV) replication activates the expression of the liver abundant host factor CIDEB with known regulatory roles in hepatic lipid homeostasis and apoptosis. We demonstrate that siRNA mediated knockdown CIDEB overexpression increase HCV replication and CIDEB knockdown inhibits HCV replication and this inhibition is independent of CIDEB's role in lipid droplet clustering and fusion.
Publication date
PublisherWiley
LanguageEnglish
AffiliationNational Research Council Canada; Medical Devices
Peer reviewedYes
NPARC number21272829
Export citationExport as RIS
Report a correctionReport a correction
Record identifier3b0ef5cf-46ad-4905-87de-bee9b6f29379
Record created2014-12-03
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)