Evidence map›Paper›PMID 40932283›Full record

ArticlemBio2025

Picornavirus 3D polymerase inhibits antiviral innate immunity by blocking the activation of JAK-STAT signaling pathway.

Kangli Li, Xiangle Zhang, Chen Liu, Guoliang Zhu, Shuo Wang, Dandan Dong, Xiaodan Wen, Weijun Chao, Baohong Liu, Ruoqing Mao and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mBio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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

20 authors.

Kangli Li *State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.ORCID 0009-0000-8862-8000
Xiangle Zhang *State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Chen LiuState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Guoliang ZhuState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Shuo WangSchool of Pharmacy, Lanzhou University, Lanzhou, China.
Dandan DongState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Xiaodan WenState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Weijun ChaoState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Baohong LiuState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Ruoqing MaoState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Yi RuState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Hong TianState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Huanan LiuState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Bo YangState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Jijun HeState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Jianhong GuoState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.
Jianye DaiSchool of Pharmacy, Lanzhou University, Lanzhou, China.
Fan YangState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.ORCID 0000-0002-8447-9594
Zixiang ZhuState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.ORCID 0000-0002-4093-9683
Haixue ZhengState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China.ORCID 0000-0001-6850-1379

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Picornaviruses are known for their rapid replication rate, which is a key characteristic that allows them to quickly infect host cells and produce progeny viruses. The interactions with host cells established by the virus to bypass host defense are essential for their rapid replication. The 3D protein, identified as the RNA-dependent RNA polymerase (RdRp) of picornaviruses, is central to viral replication. In this study, we delineated a conserved strategy employed by picornavirus 3D proteins to counteract the antiviral response elicited by interferons. Senecavirus A (SVA) 3D protein targets and hijacks JAK1, a pivotal component of the innate immune cascade, thereby decreasing the expression of a spectrum of interferon-stimulated antiviral genes. The interaction between the N-terminal region of SVA 3D (amino acids 1-152) and the FERM domain of JAK1 is responsible for the suppression of JAK-STAT signaling. Mechanistically, SVA 3D recruits the E3 ubiquitin ligase RNF125, inducing the K48-linked polyubiquitination of JAK1 at K205 and K249, which ultimately leads to the proteasomal degradation of JAK1. 3D proteins from other picornaviruses (FMDV, EMCV, and EV71) also suppress JAK1-mediated antiviral response. Collectively, these findings elucidate the suppressive regulatory mechanisms of picornaviruses 3D, highlighting a prevalent immune evasion tactic among picornaviruses, which will provide insights for developing antiviral strategies against picornaviruses.IMPORTANCEPicornaviruses can establish interactions with host cells to bypass host defense mechanisms. The highly conserved viral polymerase 3D protein of picornavirus broadly inhibited JAK-STAT signaling and promoted viral replication. Specifically, SVA 3D induces the K48-linked ubiquitination of JAK1 through recruitment of the E3 ubiquitin ligase RNF125. Similarly, FMDV, EMCV, and EV71 3D proteins act as negative regulators to inhibit JAK-STAT pathway activation. These findings unveil a common immune suppression strategy employed by picornaviruses, thereby advancing our understanding of picornavirus pathogenesis and opening avenues for developing antiviral strategies against picornaviruses.

Indexed as

Immunity, InnateJanus Kinase 1Janus KinasesPicornaviridaeRNA-Dependent RNA PolymeraseSignal TransductionSTAT Transcription FactorsViral Nonstructural ProteinsHost-Pathogen InteractionsHumansImmune EvasionVirus ReplicationJAK1 protein, humanJanus Kinase 1Janus KinasesRNA-Dependent RNA PolymeraseSTAT Transcription FactorsViral Nonstructural Proteins3D proteininnate immune responseJAK1picornavirusRNF125ubiquitination

Identifiers

PMID40932283
PMCPMC12506094

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Registered trials

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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.