Dampened STING-Dependent Interferon Activation in Bats

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, wheth...

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Published inCell Host & Microbe Vol. 23; no. 3; pp. 297 - 301.e4
Main Authors Xie, Jiazheng, Li, Yang, Shen, Xurui, Goh, Geraldine, Zhu, Yan, Cui, Jie, Wang, Lin-Fa, Shi, Zheng-Li, Zhou, Peng
Format Journal Article Web Resource
LanguageEnglish
Published United States Elsevier Inc 14.03.2018
Elsevier BV
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Abstract 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. [Display omitted] •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.
AbstractList 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. [Display omitted] •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.
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.
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.
Author Xie, Jiazheng
Li, Yang
Cui, Jie
Shi, Zheng-Li
Wang, Lin-Fa
Shen, Xurui
Goh, Geraldine
Zhou, Peng
Zhu, Yan
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Issue 3
Keywords bats
STING
dampened
interferon
virus
DNA sensing
Language English
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PublicationDecade 2010
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PublicationPlace_xml – name: United States
– name: Amsterdam
PublicationTitle Cell Host & Microbe
PublicationTitleAlternate Cell Host Microbe
PublicationYear 2018
Publisher Elsevier Inc
Elsevier BV
Publisher_xml – name: Elsevier Inc
– name: Elsevier BV
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Snippet 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...
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SubjectTerms Animals
bats
Brief Report
Cell Line
Chiroptera - genetics
Chiroptera - immunology
Chiroptera - virology
Cytoplasm - virology
Cytosol - metabolism
dampened
Disease Reservoirs
DNA Damage
DNA sensing
DNA, Viral - metabolism
DNA-Binding Proteins
Gene Expression
HEK293 Cells
Humans
interferon
Interferons - metabolism
Membrane Proteins - genetics
Membrane Proteins - immunology
Membrane Proteins - metabolism
Mice
Mice, Inbred BALB C
Mutation
Nuclear Proteins - metabolism
Phosphoproteins - metabolism
Sendai virus
Sequence Analysis, RNA
STING
Toll-Like Receptor 9 - immunology
virus
Virus Diseases - immunology
Virus Diseases - veterinary
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Title Dampened STING-Dependent Interferon Activation in Bats
URI https://dx.doi.org/10.1016/j.chom.2018.01.006
https://www.ncbi.nlm.nih.gov/pubmed/29478775
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