2. Academic Validation
  3. Herpes simplex virus type 1 disseminates from the cornea to the CNS in mice by thwarting type III interferon immune defenses

Herpes simplex virus type 1 disseminates from the cornea to the CNS in mice by thwarting type III interferon immune defenses

  • Cell Rep. 2025 Nov 18;44(12):116581. doi: 10.1016/j.celrep.2025.116581.
Jian Zhou 1,  Xiaomei Xiao 2,  Wenhao Sun 2,  Wenqiang Yu 2,  Chenghui Liao 2,  Liang Ye 3
Affiliations

Affiliations

  • 1 Department of Immunology, International Cancer Center, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong Province 518055, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong Province 518055, China.
  • 2 Department of Immunology, International Cancer Center, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong Province 518055, China.
  • 3 Department of Immunology, International Cancer Center, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong Province 518055, China. Electronic address: [email protected].
PMID: 41259200 DOI: 10.1016/j.celrep.2025.116581
Abstract

Herpes simplex virus type 1 (HSV-1) can spread to the central nervous system (CNS) through the cornea to induce neurological diseases, but how HSV-1 overcomes corneal innate immunity to enter the CNS remains unclear. We report that HSV-1-infected cell protein 0 (ICP0) upregulates corneal suppressor of cytokine signaling 1 (SOCS1) and SOCS3 expression, which inhibits stimulator of interferon genes (STING)-interferon-λ (IFN-λ) signaling to promote virus escape to the CNS. Mechanistically, SOCS3 interacts with STING and induces K48-linked ubiquitination of STING at Lys275, which promotes STING degradation, ultimately suppressing corneal IFN-λ production. SOCS1 inhibits STAT1 activation against corneal IFN-λ Antiviral responses. Administration of a STING agonist or IFN-λ preserves the corneal epithelial barrier and limits viral dissemination to the CNS. These findings elucidate an HSV-1 immune evasion mechanism in the cornea and highlight the potential of enhancing IFN-λ responses to prevent viral propagation to the CNS.

Keywords

CP: microbiology; CP: neuroscience; HSV-1; IFN-λ; SOCS1/3; STAT1; STING; central nervous system.

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