Dampened STING-Dependent Interferon Activation in Bats.
Dampened STING-Dependent Interferon Activation in Bats.
复制标题
抑制蝙蝠中 STING 依赖性干扰素激活
DOI：
10.1016/j.chom.2018.01.006
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发表时间：
2018-03-14
影响因子：
30.3
通讯作者：
Zhou P
中科院分区：
文献类型：
--
作者：
Xie J;Li Y;Shen X;Goh G;Zhu Y;Cui J;Wang LF;Shi ZL;Zhou P
与陆地哺乳动物相比，蝙蝠的寿命更长，与各种病毒共存的能力也更强。除了这些病毒感染产生的胞浆DNA外，飞行的代谢需求还会导致DNA损伤和自身DNA释放到细胞质中。然而，蝙蝠是否有改变的DNA传感/防御系统来平衡细胞内高水平的DNA仍然是一个悬而未决的问题。我们证明蝙蝠对干扰素的反应受到抑制，这是由于STING中高度保守的丝氨酸残基(S358)的替换，STING是多个DNA传感途径中的一种基本适配器蛋白。通过引入S358来逆转这种突变，恢复了STIN功能，导致干扰素激活和病毒抑制。结合之前关于其他DNA传感器如TLR9、IFI16和AIM2的蝙蝠特异性变化的报告，我们的发现揭示了蝙蝠对飞行的适应、它们的长寿命以及它们作为病毒库的独特能力。蝙蝠体内高度保守的丝氨酸残基(S358)被替换为蝙蝠刺，这一突变逆转了蝙蝠的刺痛功能，干扰素激活和病毒抑制蝙蝠与多种病毒共存，感染衍生的胞浆DNA可能导致DNA感知增强和过度激活。谢等人。结果表明，由于高度保守和功能重要的丝氨酸残基S358的替换，蝙蝠体内依赖刺的干扰素活性受到抑制。
Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways. Reversing this mutation by introducing S358 restored STING functionality, resulting in interferon activation and virus inhibition. Combined with previous reports on bat-specific changes of other DNA sensors such as TLR9, IFI16, and AIM2, our findings shed light on bat adaptation to flight, their long lifespan, and their unique capacity to serve as a virus reservoir. STING-dependent IFN activation is dampened in bats Highly conserved serine residue (S358) is replaced in bat STING Reversing this mutation restores STING function, IFN activation, and virus inhibition Bats co-exist with a large variety of viruses, and infection-derived cytosolic DNA could result in heightened DNA sensing and overactivation. Xie et al. show that STING-dependent IFN activation is dampened in bats due to the replacement of the highly conserved and functionally important serine residue S358.
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影响因子：
15.9
作者：
Brook CE;Dobson AP
通讯作者：
Dobson AP
DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.3
作者：
Kerur N;Veettil MV;Sharma-Walia N;Bottero V;Sadagopan S;Otageri P;Chandran B
通讯作者：
Chandran B
DOI：
10.1073/pnas.1203405109
发表时间：
2012-07-17
影响因子：
11.1
作者：
Li, Ying;Chen, Rui;Shu, Hong-Bing
通讯作者：
Shu, Hong-Bing
影响因子：
32.4
作者：
Tsuchida, Tetsuo;Zou, Jian;Akira, Shizuo
通讯作者：
Akira, Shizuo