[Battle with herpes for 37 years]

Area of Science:

• Ophthalmology and Virology
• Molecular Biology and Immunology

Context:

• Herpes simplex virus type 1 (HSV-1) establishes lifelong latency, primarily in the trigeminal ganglion, with reactivation leading to herpetic keratitis.
• Reactivation triggers include stress, UV radiation, and immunosuppression, causing epithelial, stromal, or combined forms of keratitis with significant recurrence rates (47%).
• Current treatments for epithelial herpetic keratitis involve prolonged antiviral eye ointments, questioning the necessity of such long durations.

Purpose:

• To investigate the clinical characteristics and recurrence patterns of herpetic keratitis.
• To evaluate the efficacy of shorter antiviral treatment durations for HSV-1 epithelial keratitis in a mouse model.
• To confirm HSV-1 latency in human corneas and explore the role of other herpesviruses (HHV-6, HHV-7) and immune responses in keratitis pathogenesis.

Summary:

• Analysis of 129 herpetic keratitis cases revealed epithelial (50%) and stromal (23%) types, with 47% recurrence.
• Short-term (5-day) antiviral treatments (acyclovir, valaciclovir, famciclovir) effectively reduced HSV-1 DNA in mouse ocular tissues.
• HSV-1 latency was confirmed in human corneas, and multiplex PCR detected HSV-1, HHV-6, and HHV-7 DNA in ocular samples.
• Inhibiting NF-κB reduced HSV-1 DNA in trigeminal ganglia, while chemokine analysis indicated Th1 and Th17 responses are involved in herpetic keratitis.

Impact:

• Findings suggest shorter antiviral courses may be sufficient for epithelial herpetic keratitis, potentially reducing treatment burden.
• Demonstration of HSV-1 latency in the cornea and co-detection of other herpesviruses highlight complex viral interactions in ocular infections.
• Understanding the role of Th17 immune response offers potential therapeutic targets for preventing herpetic keratitis recurrence.