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    IFI16 is an innate immune sensor for intracellular DNA

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    Authors
    Unterholzner, Leonie
    Keating, Sinead E.
    Baran, Marcin
    Horan, Kristy A.
    Jensen, Soren B.
    Sharma, Shrutie
    Sirois, Cherilyn M.
    Jin, Tengchuan
    Latz, Eicke
    Xiao, T. Sam
    Fitzgerald, Katherine A.
    Paludan, Soren R.
    Bowie, Andrew G.
    Show allShow less
    UMass Chan Affiliations
    Department of Medicine, Division of Infectious Diseases and Immunology
    Document Type
    Journal Article
    Publication Date
    2010-11-05
    Keywords
    Animals
    Cell Line
    DNA, Viral
    Herpesvirus 1, Human
    Humans
    *Immunity, Innate
    Interferon-beta
    Intracellular Space
    Membrane Proteins
    Mice
    Monocytes
    Nuclear Proteins
    Phosphoproteins
    Signal Transduction
    Immunology and Infectious Disease
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    Link to Full Text
    http://dx.doi.org/10.1038/ni.1932
    Abstract
    The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor that mediates the induction of interferon-beta (IFN-beta). IFI16 directly associated with IFN-beta-inducing viral DNA motifs. STING, a critical mediator of IFN-beta responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-kappaB induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-beta induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).
    Source
    Nat Immunol. 2010 Nov;11(11):997-1004. Epub 2010 Oct 3. Link to article on publisher's site
    DOI
    10.1038/ni.1932
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/34886
    PubMed ID
    20890285
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1038/ni.1932
    Scopus Count
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