Title |
Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA
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Published in |
Nature Immunology, September 2015
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DOI | 10.1038/ni.3267 |
Pubmed ID | |
Authors |
Anna-Maria Herzner, Cristina Amparo Hagmann, Marion Goldeck, Steven Wolter, Kirsten Kübler, Sabine Wittmann, Thomas Gramberg, Liudmila Andreeva, Karl-Peter Hopfner, Christina Mertens, Thomas Zillinger, Tengchuan Jin, Tsan Sam Xiao, Eva Bartok, Christoph Coch, Damian Ackermann, Veit Hornung, Janos Ludwig, Winfried Barchet, Gunther Hartmann, Martin Schlee |
Abstract |
Cytosolic DNA that emerges during infection with a retrovirus or DNA virus triggers antiviral type I interferon responses. So far, only double-stranded DNA (dsDNA) over 40 base pairs (bp) in length has been considered immunostimulatory. Here we found that unpaired DNA nucleotides flanking short base-paired DNA stretches, as in stem-loop structures of single-stranded DNA (ssDNA) derived from human immunodeficiency virus type 1 (HIV-1), activated the type I interferon-inducing DNA sensor cGAS in a sequence-dependent manner. DNA structures containing unpaired guanosines flanking short (12- to 20-bp) dsDNA (Y-form DNA) were highly stimulatory and specifically enhanced the enzymatic activity of cGAS. Furthermore, we found that primary HIV-1 reverse transcripts represented the predominant viral cytosolic DNA species during early infection of macrophages and that these ssDNAs were highly immunostimulatory. Collectively, our study identifies unpaired guanosines in Y-form DNA as a highly active, minimal cGAS recognition motif that enables detection of HIV-1 ssDNA. |
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Mendeley readers
Geographical breakdown
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Student > Master | 25 | 9% |
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Chemistry | 10 | 4% |
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