Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA

Herzner AM, Hagmann CA, Goldeck M, Wolter S, Kuebler K, Wittmann S, Gramberg T, Andreeva L, Hopfner KP, Mertens C, Zillinger T, Jin T, Xiao TS, Bartok E, Coch C, Ackermann D, Hornung V, Ludwig J, Barchet W, Hartmann G, Schlee M (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Nature Immunology Nature Research

Book Volume: 16

Pages Range: 1025-33

Journal Issue: 10

DOI: 10.1038/ni.3267

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.

Authors with CRIS profile

Thomas Gramberg Institute of Clinical and Molecular Virology

Involved external institutions

Universitätsklinikum Bonn DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Case Western Reserve University US United States (USA) (US) University of Science and Technology of China (USTC) CN China (CN) Ludwig-Maximilians-Universität (LMU) DE Germany (DE)

How to cite

APA:

Herzner, A.-M., Hagmann, C.A., Goldeck, M., Wolter, S., Kuebler, K., Wittmann, S.,... Schlee, M. (2015). Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA. Nature Immunology, 16(10), 1025-33. https://dx.doi.org/10.1038/ni.3267

MLA:

Herzner, Anna-Maria, et al. "Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA." Nature Immunology 16.10 (2015): 1025-33.

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