Double-stranded DNA and double-stranded RNA induce a common antiviral signaling pathway in human cells.
Virus infection triggers IFN immune defenses in infected cells in part through viral nucleic acid interactions, but the pathways by which dsDNA and DNA viruses trigger innate defenses are only partially understood. Here we present evidence that both retinoic acid-induced gene I (RIG-I) and mitochondrial antiviral signaling protein (MAVS) are required for dsDNA-induced IFN-beta promoter activation in a human hepatoma cell line (Huh-7), and that activation is efficiently blocked by the hepatitis C virus NS3/4A protease, which is known to block dsRNA signaling by cleaving MAVS. These findings suggest that dsDNA and dsRNA share a common pathway to trigger the innate antiviral defense response in human cells, although dsDNA appears to trigger that pathway upstream of the dsRNA-interacting protein RIG-I.
Cheng
Guofeng
G
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Zhong
Jin
J
Chung
Josan
J
Chisari
Francis V
FV
D000998:Antiviral Agents; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012330:RNA, Double-Stranded / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic; D015398:Signal Transduction; D018139:Simplexvirus / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; D004247:DNA; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases