CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, 100049 Beijing, China.
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore.
Cell Host Microbe. 2018 Mar 14;23(3):297-301.e4. doi: 10.1016/j.chom.2018.01.006. Epub 2018 Feb 22.
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.
与陆地哺乳动物相比，蝙蝠具有更长的寿命和更大的能力与多种病毒共存。除了这些病毒感染产生的细胞质 DNA 外，飞行的代谢需求还会导致 DNA 损伤，并将自身 DNA 释放到细胞质中。然而，蝙蝠是否具有改变的 DNA 感应/防御系统来平衡高细胞质 DNA 水平仍然是一个悬而未决的问题。我们证明，由于 STING 中高度保守的丝氨酸残基（S358）被替换，蝙蝠的干扰素反应受到抑制，STING 是多种 DNA 感应途径中的必需衔接蛋白。通过引入 S358 逆转这种突变恢复了 STING 的功能，导致干扰素的激活和病毒的抑制。结合之前关于其他 DNA 传感器（如 TLR9、IFI16 和 AIM2）在蝙蝠中的特异性变化的报告，我们的发现揭示了蝙蝠对飞行、长寿以及作为病毒储存库的独特能力的适应机制。
