title: Transcriptional analysis of antiviral small molecule therapeutics as agonists of the RLR pathway.
abstract: The recognition of pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRR) during viral infection initiates the induction of antiviral signaling pathways, including activation of the Interferon Regulator Factor 3 (IRF3). We identified small molecule compounds that activate IRF3 through MAVS, thereby inhibiting infection by viruses of the families Flaviviridae (West Nile virus, dengue virus and hepatitis C virus), Filoviridae (Ebola virus), Orthomyxoviridae (influenza A virus), Arenaviridae (Lassa virus) and Paramyxoviridae (respiratory syncytial virus, Nipah virus) (1). In this study, we tested a lead compound along with medicinal chemistry-derived analogs to compare the gene transcriptional profiles induced by these molecules to that of other known MAVS-dependent IRF3 agonists. Transcriptional analysis of these small molecules revealed the induction of specific antiviral genes and identified a novel module of host driven immune regulated genes that suppress infection of a range of RNA viruses. Microarray data can be found in Gene Expression Omnibus (GSE74047).
authors.affiliation: Department of Immunology, and the Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, WA, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Green
authors.affiliation: Department of Immunology, and the Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, WA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wilkins
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Pattabhi
authors.affiliation: Department of Immunology, and the Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, WA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Dong
authors.affiliation: Department of Immunology, and the Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, WA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Loo
authors.affiliation: Department of Immunology, and the Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gale
keywords: Anti-viral; IRF-3; Immunity; Innate; RIG-I