Evidence map›Paper›PMID 36745686›Full record

ArticlePLoS pathogens2023

Innate sensing of picornavirus infection involves cGAS-STING-mediated antiviral responses triggered by mitochondrial DNA release.

Huisheng Liu, Zixiang Zhu, Qiao Xue, Fan Yang, Zongqiang Li, Zhaoning Xue, Weijun Cao, Jijun He, Jianhong Guo, Xiangtao Liu and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
13.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 80 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Huisheng LiuState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Zixiang ZhuState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Qiao XueState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Fan YangState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Zongqiang LiState Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
Zhaoning XueState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Weijun CaoState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Jijun HeState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Jianhong GuoState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Xiangtao LiuState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Andrew E ShawThe Pirbright Institute, Pirbright, Surrey, United Kingdom.
Donald P KingThe Pirbright Institute, Pirbright, Surrey, United Kingdom.
Haixue ZhengState Key Laboratory of Veterinary Etiological Biology; College of Veterinary Medicine, Lanzhou University, WOAH/National reference laboratory for foot-and-mouth disease; Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.ORCID 0000-0002-1644-2300
Lanzhou Veterinary Research Institute · CNThe Pirbright Institute · GBState Key Laboratory of Membrane Biology

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cyclic GMP-AMP synthase (cGAS) plays a key role in the innate immune responses to both DNA and RNA virus infection. Here, we found that enterovirus 71 (EV-A71), Seneca Valley virus (SVV), and foot-and-mouth disease virus (FMDV) infection triggered mitochondria damage and mitochondrial DNA (mtDNA) release in vitro and vivo. These responses were mediated by picornavirus 2B proteins which induced mtDNA release during viral replication. SVV infection caused the opening of mitochondrial permeability transition pore (mPTP) and led to voltage-dependent anion channel 1 (VDAC1)- and BCL2 antagonist/killer 1 (Bak) and Bak/BCL2-associated X (Bax)-dependent mtDNA leakage into the cytoplasm, while EV-A71 and FMDV infection induced mPTP opening and resulted in VDAC1-dependent mtDNA release. The released mtDNA bound to cGAS and activated cGAS-mediated antiviral immune response. cGAS was essential for inhibiting EV-A71, SVV, and FMDV replication by regulation of IFN-β production. cGAS deficiency contributed to higher mortality of EV-A71- or FMDV-infected mice. In addition, we found that SVV 2C protein was responsible for decreasing cGAS expression through the autophagy pathway. The 9th and 153rd amino acid sites in 2C were critical for induction of cGAS degradation. Furthermore, we also show that EV-A71, CA16, and EMCV 2C antagonize the cGAS-stimulator of interferon genes (STING) pathway through interaction with STING, and highly conserved amino acids Y155 and S156 were critical for this inhibitory effect. In conclusion, these data reveal novel mechanisms of picornaviruses to block the antiviral effect mediated by the cGAS-STING signaling pathway, which will provide insights for developing antiviral strategies against picornaviruses.

Indexed as

Foot-and-Mouth Disease VirusPicornaviridae InfectionsAnimalsAntiviral AgentsDNA, MitochondrialImmunity, InnateInterferon-betaMiceMitochondriaNucleotidyltransferasesPicornaviridaeProto-Oncogene Proteins c-bcl-2STING ProteinAntiviral AgentsDNA, MitochondrialInterferon-betaNucleotidyltransferasesProto-Oncogene Proteins c-bcl-2Sting1 protein, mouseSTING Protein

Identifiers

PMID36745686
PMCPMC9934381
OpenAlexW4319293747

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.