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.
Copyright © 2019 American Society for Microbiology.
MeSH terms
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ATP Binding Cassette Transporter 1 / antagonists & inhibitors
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ATP Binding Cassette Transporter 1 / genetics*
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ATP Binding Cassette Transporter 1 / metabolism
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ATP Binding Cassette Transporter, Subfamily G, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily G, Member 1 / metabolism
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Antiviral Agents / pharmacology*
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Apolipoproteins E / genetics
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Apolipoproteins E / metabolism
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Chikungunya virus / drug effects*
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Chikungunya virus / growth & development
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Chikungunya virus / metabolism
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Cholesterol / metabolism
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Cholesterol / pharmacology
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Fibroblasts / drug effects*
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Fibroblasts / metabolism
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Fibroblasts / virology
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Gene Expression Regulation
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Host-Pathogen Interactions / drug effects*
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Humans
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Indazoles / pharmacology*
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Interferons / genetics
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Interferons / metabolism
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Liver X Receptors / antagonists & inhibitors
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Liver X Receptors / genetics*
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Liver X Receptors / metabolism
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Primary Cell Culture
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Signal Transduction
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Virus Replication / drug effects
Substances
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2-(2-chloro-4-fluorobenzyl)-3-(4-fluorophenyl)-7-(trifluoromethyl)-2H-indazole
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ABCA1 protein, human
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ABCG1 protein, human
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ATP Binding Cassette Transporter 1
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ATP Binding Cassette Transporter, Subfamily G, Member 1
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Antiviral Agents
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Apolipoproteins E
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Indazoles
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Liver X Receptors
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RNA, Small Interfering
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Interferons
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Cholesterol