Evidence map›Paper›PMID 41021645›Full record

ArticlePLoS pathogens2025

The tegument protein VP22 of pseudorabies virus inhibits cGAS condensation by inducing nuclear-to-cytoplasmic translocation of DDX21.

Kesen Liu, Wandi Cao, Hanhua Zhang, Xingmiao Yang, Chengyue Wu, Xingya Wang, Qian Sun, Jianxiong Guo, Ting Zhang, Yan Liu and 1 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

11 authors.

Kesen LiuKey Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Wandi CaoKey Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Hanhua ZhangKey Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Xingmiao YangGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen, China.
Chengyue WuKey Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Xingya WangKey Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Qian SunGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen, China.
Jianxiong GuoChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
Ting ZhangShenzhen Health Administrative Center for Cadre and Talent, Shenzhen, China.
Yan LiuChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
Xing LiuKey Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.ORCID 0000-0003-3655-5000

Funding

Jiangsu Independent Innovation Fund ProjectNational Natural Science Foundation of ChinaNatural Science Foundation of Jiangsu Province
6 · The paper itself

Abstract

Cyclic GMP-AMP synthase (cGAS) is a pivotal DNA sensor that initiates antiviral responses, yet the mechanisms by which viruses evade cGAS-mediated innate immunity remain poorly understood. Here, we identified VP22, a tegument protein of pseudorabies virus (PRV), a member of the Alphaherpesvirinae subfamily, as a viral antagonist of the type I interferon (IFN-I) response through hijacking the host RNA helicase DDX21. Specifically, VP22 impairs 2'3'-cyclic GMP-AMP (cGAMP) synthesis by disrupting cGAS condensation. In vivo, cGAS restricts the replication of VP22-deficient PRV and attenuates its pathogenicity, an effect neutralized by VP22. Notably, DDX21 is essential for VP22-mediated inhibition of cGAS activity. Mechanistically, VP22 stabilizes DDX21 protein level and enhances its interaction with cGAS. Furthermore, VP22 promotes the translocation of DDX21 from the nucleus to the cytoplasm, a process required for inhibition of cGAS condensation and activation. Collectively, these findings reveal a previously unrecognized, host-dependent mechanism by which PRV subverts cGAS signaling, shedding light on viral strategies to subvert host DNA sensing and innate immunity.

Indexed as

DEAD-box RNA HelicasesHerpesvirus 1, SuidNucleotidyltransferasesPseudorabiesViral Structural ProteinsAnimalsCell NucleusCytoplasmHEK293 CellsHumansImmunity, InnateMiceSwineVirus ReplicationDEAD-box RNA HelicasesNucleotidyltransferasesViral Structural Proteins

Identifiers

PMID41021645
PMCPMC12503277

What OpenQuestion holds

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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.