Dampened STING-Dependent Interferon Activation in Bats
| Autor: | Geraldine Goh, Jiazheng Xie, Lin-Fa Wang, Peng Zhou, Yang Li, Yan Zhu, Jie Cui, Zhengli Shi, Xu-Rui Shen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cytoplasm Gene Expression dampened medicine.disease_cause Sendai virus Mice chemistry.chemical_compound Cytosol 0302 clinical medicine Interferon Chiroptera Mice Inbred BALB C Mutation Nuclear Proteins interferon Cell biology DNA-Binding Proteins Virus Diseases DNA sensing medicine.drug DNA damage bats virus Biology Microbiology Article Virus Cell Line 03 medical and health sciences AIM2 Virology medicine Animals Humans Disease Reservoirs IFI16 Sequence Analysis RNA Membrane Proteins Phosphoproteins Sting HEK293 Cells 030104 developmental biology chemistry Toll-Like Receptor 9 DNA Viral Parasitology Interferons 030217 neurology & neurosurgery DNA DNA Damage STING |
| Zdroj: | Cell Host & Microbe |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2018.01.006 |
| Popis: | Summary 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. Graphical Abstract Highlights • 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. |
| Databáze: | OpenAIRE |
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