Cytokine-independent upregulation of MDA5 in viral infection.
The RNA helicases RIG-I and MDA5 detect virus infection of dendritic cells (DCs) leading to cytokine induction. Maximal sensitivity for virus detection by these helicases is obtained after their upregulation, which is thought to occur primarily through type I interferon (IFN) signaling. Here we demonstrate that in response to paramyxovirus infection, RIG-I upregulation requires type I IFN whereas MDA5 expression is increased by Sendai virus infection independently of signaling mediated by type I IFN, STAT1, tumor necrosis factor alpha, or NF-kappaB. This MDA5 upregulation is largely lost in IRF3 knockout DCs and is achieved in type I IFN-deficient cells expressing constitutively active IRF3.
Yount
Jacob S
JS
Department of Microbiology, The Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
Moran
Thomas M
TM
López
Carolina B
CB
D000818:Animals; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D050838:Interferon Regulatory Factor-3 / Q000172:deficiency / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D007371:Interferon-gamma / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology; D011956:Receptors, Cell Surface; D010253:Respirovirus Infections / Q000235:genetics / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000172:deficiency / Q000276:immunology; D029082:Sendai virus / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*; D000097905:Roundabout Proteins
D053487:DEAD-box RNA Helicases; D050838:Interferon Regulatory Factor-3; D000072640:Interferon-Induced Helicase, IFIH1; D007371:Interferon-gamma; D008565:Membrane Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; C494233:Irf3 protein, mouse; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C494080:Stat1 protein, mouse; C510592:Ifih1 protein, mouse