Inhibition of Chikungunya Virus Replication in Primary Human Fibroblasts by Liver X Receptor Agonist

Antimicrob Agents Chemother. 2019 Aug 23;63(9):e01220-19. doi: 10.1128/AAC.01220-19. Print 2019 Sep.

Abstract

The mosquito-borne chikungunya virus (CHIKV) causes acute pain and joint inflammation, and in recent years the virus has caused large epidemics in previously CHIKV-free geographic areas. To advance the understanding of host factors that antagonize CHIKV, we show that synthetic agonist of liver X receptor (LXR-623) inhibits CHIKV replication by upregulating the cholesterol exporter ABCA1 and that endogenous and pharmacological activation of interferon signaling pathway partners with LXR-623 to generate a superior antiviral state.

Keywords: LXR; chikungunya; host-targeting antiviral; virus.

MeSH terms

  • ATP Binding Cassette Transporter 1 / antagonists & inhibitors
  • ATP Binding Cassette Transporter 1 / genetics*
  • ATP Binding Cassette Transporter 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / metabolism
  • Antiviral Agents / pharmacology*
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Chikungunya virus / drug effects*
  • Chikungunya virus / growth & development
  • Chikungunya virus / metabolism
  • Cholesterol / metabolism
  • Cholesterol / pharmacology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / virology
  • Gene Expression Regulation
  • Host-Pathogen Interactions / drug effects*
  • Humans
  • Indazoles / pharmacology*
  • Interferons / genetics
  • Interferons / metabolism
  • Liver X Receptors / antagonists & inhibitors
  • Liver X Receptors / genetics*
  • Liver X Receptors / metabolism
  • Primary Cell Culture
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Virus Replication / drug effects

Substances

  • 2-(2-chloro-4-fluorobenzyl)-3-(4-fluorophenyl)-7-(trifluoromethyl)-2H-indazole
  • ABCA1 protein, human
  • ABCG1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • Antiviral Agents
  • Apolipoproteins E
  • Indazoles
  • Liver X Receptors
  • RNA, Small Interfering
  • Interferons
  • Cholesterol