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Updated: Jun 19, 2026
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Ex Vivo Organotypic Corneal Model of Acute Epithelial Herpes Simplex Virus Type I Infection
Published on: November 3, 2012
Time-Course Transcriptomic Analysis Reveals PANoptosis-CCL2 Axis in Herpes Simplex Keratitis.
Changyu Wu1, Junwen Ouyang1, Yaoyao Liu1
1Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Investigative Ophthalmology & Visual Science
|June 18, 2026
Summary
Herpes simplex keratitis involves sequential immune responses and programmed cell death (PCD), with PANoptosis amplifying antiviral immunity. Targeting the PANoptosis-CCL2/CCR2 axis offers a potential therapeutic strategy for HSK.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Herpes simplex virus type 1 (HSV-1) causes herpes simplex keratitis (HSK), a significant ocular infection.
- Understanding the interplay between immune responses and programmed cell death (PCD) is crucial for HSK pathogenesis.
- PANoptosis, an integrated form of PCD, has emerged as a key cellular process in various inflammatory conditions.
Purpose of the Study:
- To characterize the temporal dynamics of corneal immune responses and PCD after HSV-1 infection.
- To investigate the specific role of PANoptosis in modulating immune responses during HSK.
- To identify potential therapeutic targets within the identified pathways.
Main Methods:
- Established a murine model of HSK induced by HSV-1 infection.
- Performed time-course RNA sequencing on infected murine corneas.
- Utilized quantitative real-time PCR, western blotting, immunofluorescence, flow cytometry, and co-culture experiments for mechanistic analysis.
- Assessed PCD pathways using antagonists targeting PANoptosis.
Main Results:
- Identified sequential immune response phases: homeostasis disruption, immune amplification, and tissue reorganization.
- Demonstrated that the immune amplification phase involves apoptosis, pyroptosis, and necroptosis, culminating in PANoptosis.
- Confirmed Z-DNA-binding protein 1 (ZBP1) as a driver of PANoptosome formation in HSK.
- Showed that PANoptosis promotes C-C motif chemokine ligand 2 (CCL2) release, enhancing macrophage activation and migration via the CCL2/CCR2 axis.
- Found that the PANoptosis-CCL2/CCR2 axis is upregulated in infected corneas and can be suppressed by inhibitors.
Conclusions:
- HSK pathogenesis involves a temporal coordination between immune activation and PANoptosis.
- PANoptosis plays a critical role in amplifying antiviral immune responses during HSK.
- The ZBP1-PANoptosome-mediated PANoptosis-CCL2/CCR2 axis represents a promising therapeutic target for HSK treatment.
