title: Targeting host lipid synthesis and metabolism to inhibit dengue and hepatitis C viruses.
abstract: Lipids are necessary for every step in the replication cycle of hepatitis C virus (HCV) and dengue virus (DENV), members of the family Flaviviridae. Recent studies have demonstrated that discrete steps in the replication cycles of these viruses can be inhibited by pharmacological agents that target host factors mediating lipid synthesis, metabolism, trafficking, and signal transduction. Despite this, targeting host lipid metabolism and trafficking as an antiviral strategy by blockade of entire pathways may be limited due to host toxicity. Knowledge of the molecular details of lipid structure and function in replication and the mechanisms whereby specific lipids are generated and trafficked to the relevant sites may enable more targeted antiviral strategies without global effects on the host cell. In this review, we discuss lipids demonstrated to be critical to the replication cycles of HCV and DENV and highlight potential areas for anti-viral development. This review article forms part of a symposium on flavivirus drug discovery in Antiviral Research.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Villareal
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Rodgers
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Costello
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA. Electronic address: priscilla_yang@hms.harvard.edu.
authors.forename: Priscilla L
authors.initials: PL
authors.lastname: Yang
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D003715:Dengue / Q000188:drug therapy* / Q000378:metabolism*; D003716:Dengue Virus / Q000502:physiology*; D055808:Drug Discovery; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000096:biosynthesis / Q000235:genetics; D058990:Molecular Targeted Therapy; D015398:Signal Transduction; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D008055:Lipids
keywords: Antiviral therapy; Dengue virus; Flavivirus; Hepatitis C virus; Host-targeted antiviral; Lipids