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果蝇通过两种cGAS样受体产生抗病毒免疫
2021-07-18 14:35

两种环状GMP-AMP(cGAMP) 合酶 (cGAS)样受体可诱导果蝇抗病毒免疫,这一成果由丹麦奥胡斯大学Rune Hartmann、广州医科大学Jean-Luc Imler和Hua Cai小组经过不懈努力而取得。2021年7月14日,国际学术期刊《自然》在线发表了这一成果。

研究人员在果蝇中鉴定了两种新型cGAS样受体(cGLR)。研究表明cGLR1和cGLR2可以激活Sting和NF-κB依赖的抗病毒免疫,以应对RNA或DNA病毒感染。cGLR1感知dsRNA激活产生新的CDN 3'2'-cGAMP,而cGLR2通过产生2'3'-cGAMP 和3'2' cGAMP 来应答未知刺激因子。该研究表明cGAS是通过产生环状二核苷酸 (CDN) 而非 2'3'-cGAM感知不同核酸刺激引发免疫的受体家族成员之一。

研究人员表示,在哺乳动物细胞中,cGAS感知胞质DNA产生CDN 2'3'-cGAMP,从而引发抗病毒免疫反应。cGAS属于cGAS/DncV样核苷酸转移酶家族,其存在于原核生物和真核生物中。在细菌中,这些酶合成一系列环状寡核苷酸,是抵抗噬菌体感染的重要调节因子。

附:英文原文

Title: Two cGAS-like receptors induce antiviral immunity in Drosophila

Author: Andreas Holleufer, Kasper Grnbjerg Winther, Hans Henrik Gad, Xianlong Ai, Yuqiang Chen, Lihua Li, Ziming Wei, Huimin Deng, Jiyong Liu, Ninna Ahlmann Frederiksen, Bine Simonsen, Line Lykke Andersen, Karin Kleigrewe, Louise Dalskov, Andreas Pichlmair, Hua Cai, Jean-Luc Imler, Rune Hartmann

Issue&Volume: 2021-07-14

Abstract: In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide (CDN) 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases, present in both prokaryotes1 and eukaryotes2–5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotide and have recently emerged as important regulators of phage infections6–8. Here, we identify two novel cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting and NF-κB dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by dsRNA to produce the novel CDN 3'2'-cGAMP whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2' cGAMP in response to a yet unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors sensing different types of nucleic acids and triggering immunity through production of CDNs beyond 2'3'-cGAMP.

DOI: 10.1038/s41586-021-03800-z

Source: https://www.nature.com/articles/s41586-021-03800-z

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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