RRC ID 67116
Author Afroz S, Battu S, Giddaluru J, Khan N.
Title Dengue Virus Induced COX-2 Signaling Is Regulated Through Nutrient Sensor GCN2.
Journal Front Immunol
Abstract Nutrient sensor GCN2 plays a crucial role in the maintenance of cellular homeostasis during the condition of amino acid deprivation. Dysfunction in the GCN2 signaling underlies several chronic metabolic diseases. Recent studies highlight the anti-viral potential of GCN2 against RNA viruses such as Sindbis and HIV. However, its effect on dengue virus (DENV) pathogenesis remains poorly understood. Herein, we report that GCN2 deficient cells show increased DENV replication and viral yield in the culture supernatants compared to WT cells infected with DENV. Notably, enhanced DENV replication in GCN2-/- cells is associated with increased COX-2/PGE2 signaling. Conversely, GCN2 overexpression/activation effectively contains DENV infection by inhibiting COX-2/PGE2 signaling. Mechanistically, deletion of GCN2 triggers enhanced production of COX-2/PGE2 through profound activation of Iκκ-NF-κB signaling pathway. Altogether our results unveil a hitherto unrecognized role of GCN2 in DENV pathogenesis, thereby suggesting that targeting the GCN2 pathway might offer a novel therapeutic intervention against DENV infection.
Volume 11
Pages 1831
Published 2020-1-1
DOI 10.3389/fimmu.2020.01831
PMID 32903536
PMC PMC7438581
MeSH Cells, Cultured Cyclooxygenase 2 / metabolism* Dengue / immunology* Dengue / metabolism Dengue Virus / immunology Humans Protein Serine-Threonine Kinases / immunology* Protein Serine-Threonine Kinases / metabolism Signal Transduction / immunology*
IF 5.085
DNA material pKM2L-phPGHS2(1) (RDB05480)