期刊
NATURE IMMUNOLOGY
卷 16, 期 10, 页码 1025-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3267
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资金
- Deutsche Forschungsgemeinschaft [SFB670, DFG SCHL1930/1-1, SFB704, SFB832, KFO177]
- Deutsche Forschungsgemeinschaft Excellence Cluster ImmunoSensation
- BONFOR of the University of Bonn
- German Center of Infectious Disease
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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