Evidence map›Paper›PMID 39823515›Full record

ArticlePLoS pathogens2025

KSHV hijacks the antiviral kinase IKKε to initiate lytic replication.

Xiaoqian Wang, Zhenshan Liu, Xue Xu, Xin Wang, Zizhen Ming, Chengrong Liu, Hang Gao, Tingting Li, Qiming Liang

Abstract read
PubMed Full text at PMC Publisher
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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Xiaoqian WangInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhenshan LiuInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xue XuInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xin WangInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zizhen MingInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chengrong LiuInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hang GaoDepartment of Bone and Joint Surgery, Orthopaedic Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Tingting LiState Key Laboratory of Developmental Biology of Freshwater Fish, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Qiming LiangInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0003-4792-1547

Funding

Innovative Research Team of High-level Local Universities in ShanghaiJilin Province Science and Technology Development Plan ProjectNational Key Research and Development Project of ChinaProgram of Shanghai Academic/Technology Research LeaderShanghai Frontiers Science Center of Cellular Homeostasis and Human DiseaseShanghai Science and Technology Commission
6 · The paper itself

Abstract

IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45. This SUMOylation event leads to the association of IKKε with PML, resulting in the disruption of PML nuclear bodies (PML NBs) and subsequent increase in lytic replication of KSHV. Notably, IKKε does not affect the total expression level of PML but facilitates the translocation of PML from the nucleus to the cytoplasm during KSHV lytic replication. Further experiments utilizing mutations on the SUMOylation sites of IKKε or inhibiting IKKε using BAY-985 showed that these actions no longer impact PML NBs and completely suppress the lytic replication of KSHV. These findings not only emphasize the essential role of IKKε in the life cycle of KSHV but also illustrate how KSHV exploits IKKε through SUMOylation modification to enhance its own replication process.

Indexed as

Herpesviridae InfectionsHerpesvirus 8, HumanI-kappa B KinaseVirus ReplicationHEK293 CellsHumansImmediate-Early ProteinsNuclear ProteinsPromyelocytic Leukemia ProteinSumoylationTranscription FactorsTumor Suppressor ProteinsI-kappa B KinaseImmediate-Early ProteinsNuclear ProteinsORF45 protein, Kaposi's sarcoma-associated herpesvirusPML protein, humanPromyelocytic Leukemia ProteinTranscription FactorsTumor Suppressor Proteins

Identifiers

PMID39823515
PMCPMC11781660

What OpenQuestion holds

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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.