DNA
生物
互补DNA
逆转录病毒
碱基对
分子生物学
DNA测序
体外重组
核苷酸
病毒
病毒学
基因
生物化学
分子克隆
作者
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,János Ludwig,Winfried Barchet,Gunther Hartmann,Martin Schlee
出处
期刊:Nature Immunology
[Nature Portfolio]
日期:2015-09-07
卷期号:16 (10): 1025-1033
被引量:220
摘要
Truncated reverse transcription of HIV RNA produces a single-stranded DNA intermediate with a unique Y-DNA stem-loop structure flanked by unpaired guanines. Schlee and colleagues show this Y-DNA activates cGAS to elicit the production of type I interferon. 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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