2. Academic Validation
  3. Activation of the stress-activated protein kinase JNK in response to herpes simplex virus-1 infection coordinates transition of BRD4 from chromosome association to transcription elongation

Activation of the stress-activated protein kinase JNK in response to herpes simplex virus-1 infection coordinates transition of BRD4 from chromosome association to transcription elongation

  • J Biol Chem. 2025 Sep;301(9):110590. doi: 10.1016/j.jbc.2025.110590.
Weikang Sun 1,  Ke Ren 2,  Jingjing Li 3,  Mengyu Zhang 1,  Qishen Jiang 4,  Lingling Wang 5,  Erguang Li 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, Jiangsu, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu, China.
  • 2 School of Laboratory Medicine, Chengdu Medical College, Chengdu, China.
  • 3 Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu, China.
  • 4 State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, Jiangsu, China; College of Life Sciences, Nanjing University, Nanjing, China.
  • 5 School of Medical Informatics, Xihua University, Chengdu, Sichuan, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, Jiangsu, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu, China; Institute of Medical Virology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. Electronic address: [email protected].
PMID: 40812420 DOI: 10.1016/j.jbc.2025.110590
Abstract

The c-Jun N-terminal kinase (JNK) signaling pathway is required for herpes simplex virus 1 lytic Infection and reactivation from latency. JNK signaling regulates cellular processes in response to stress through transcriptional regulation. However, the mechanisms by which JNK regulates HSV-1 Infection are less defined. We show here that HSV-1 Infection triggers BRD4 transition from chromosome association to transcriptional regulation for viral Infection. Specifically, HSV-1 Infection induces JNK activation which mediates redistribution of BRD4, an epigenetic reader protein, from chromatin-targeting to association with proteins of transcriptional regulation. BRD4 transitions to viral Infection regulation by complexing with P-TEFb, a positive transcription elongation factor, and association with viral DNA. Genetic ablation or perturbation of JNK with chemical inhibitors or siRNA leads to impediment of BRD4 release and inhibition of HSV-1 Infection. Both chemotherapeutic agents and irradiation are known to promote JNK activation and HSV reactivation. We show further that JNK agonist or chemotherapeutic agents known to activate JNK can enhance HSV-1 Infection. Our study reveals a novel mechanism by which JNK regulates HSV-1 Infection through stress-induced BRD4 function transition from host chromosome association to viral gene expression. The work links recurrent HSV Infection by chemotherapeutic agents to JNK activation.

Keywords

BRD4 release; HSV-1; P-TEFb; bromodomain-containing protein 4; c-Jun N-terminal kinase; mitogen-activated protein kinase.

Figures