NDLI: Interferon Î³-inducible protein (IFI) 16 transcriptionally regulates type i interferons and other interferon-stimulated genes and controls the interferon response to both DNA and RNA viruses.

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Interferon Î³-inducible protein (IFI) 16 transcriptionally regulates type i interferons and other interferon-stimulated genes and controls the interferon response to both DNA and RNA viruses.

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Interferon Î³-inducible protein (IFI) 16 transcriptionally regulates type i interferons and other interferon-stimulated genes and controls the interferon response to both DNA and RNA viruses.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Atianand, Maninjay Kurt-jones, Evelyn A. Thompson, Mikayla R. Sharma, Shruti Jensen, Søren B. Carpenter, Susan Knipe, David M. Fitzgerald, Katherine A.
Description	Author Affiliation: Thompson MR ( From the Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.); Sharma S ( From the Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.); Atianand M ( From the Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.); Jensen SB ( Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark, and.); Carpenter S ( From the Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.); Knipe DM ( Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115.); Fitzgerald KA ( From the Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.); Kurt-Jones EA ( From the Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, evelyn.kurt-jones@umassmed.edu.)
Abstract	The interferon Î³-inducible protein 16 (IFI16) has recently been linked to the detection of nuclear and cytosolic DNA during infection with herpes simplex virus-1 and HIV. IFI16 binds dsDNA via HIN200 domains and activates stimulator of interferon genes (STING), leading to TANK (TRAF family member-associated NF-κB activator)-binding kinase-1 (TBK1)-dependent phosphorylation of interferon regulatory factor (IRF) 3 and transcription of type I interferons (IFNs) and related genes. To better understand the role of IFI16 in coordinating type I IFN gene regulation, we generated cell lines with stable knockdown of IFI16 and examined responses to DNA and RNA viruses as well as cyclic dinucleotides. As expected, stable knockdown of IFI16 led to a severely attenuated type I IFN response to DNA ligands and viruses. In contrast, expression of the NF-κB-regulated cytokines IL-6 and IL-1ß was unaffected in IFI16 knockdown cells, suggesting that the role of IFI16 in sensing these triggers was unique to the type I IFN pathway. Surprisingly, we also found that knockdown of IFI16 led to a severe attenuation of IFN- and the IFN-stimulated gene retinoic acid-inducible gene I (RIG-I) in response to cyclic GMP-AMP, a second messenger produced by cyclic GMP-AMP synthase (cGAS) as well as RNA ligands and viruses. Analysis of IFI16 knockdown cells revealed compromised occupancy of RNA polymerase II on the IFN- promoter in these cells, suggesting that transcription of IFN-stimulated genes is dependent on IFI16. These results indicate a broader role for IFI16 in the regulation of the type I IFN response to RNA and DNA viruses in antiviral immunity.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	34
Volume Number	289
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2014-08-22
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA Viruses Immunology Interferon Type I Physiology Nuclear Proteins Phosphoproteins RNA Viruses Transcription, Genetic DNA Primers Enzyme-Linked Immunosorbent Assay Gene Knockdown Techniques Gene Silencing HEK293 Cells Biosynthesis Genetics Polymerase Chain Reaction Research Support, N.I.H., Extramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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