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Herpes simplex virus isolation in chronic stromal keratitis: human and laboratory studies
Insights
Herpes simplex virus (HSV) was isolated from 29.4% of patients with herpetic keratitis. Virus presence in corneal scarring suggests HSV persistence, potentially via sensory nerve entry.
Area of Science:
- Ophthalmology
- Virology
- Microbiology
Background:
- Herpetic keratitis, a common cause of corneal scarring, is often caused by herpes simplex virus (HSV).
- Understanding HSV persistence mechanisms in the cornea is crucial for effective treatment and prevention of recurrent disease.
Purpose of the Study:
- To investigate the isolation of HSV from corneal tissues of patients with herpetic keratitis.
- To explore the route of HSV entry into the corneal stroma and its persistence mechanisms.
Main Methods:
- Organ culture of corneal discs from 41 patients for HSV isolation.
- Electron microscopy (EM) and peroxidase-antiperoxidase (PAP) staining for HSV detection.
- Murine model of HSV keratitis to study viral entry and persistence.
Main Results:
- HSV was isolated from 10 of 41 patients (29.4%) with herpetic keratitis.
- Virus was exclusively isolated from scarred portions of the cornea in three patients.
- EM confirmed HSV particles in stromal cells; PAP staining indicated viral entry via sensory nerves in a murine model.
Conclusions:
- HSV can be isolated from scarred corneal tissue in patients with a history of herpetic keratitis.
- Evidence suggests HSV accesses the corneal stroma via sensory nerves, facilitating long-term persistence.
- Direct corneal inoculation did not lead to persistent infection, unlike nerve-mediated entry.
Abstract:
The corneal discs of 41 patients with scarring reminiscent of herpetic infection were organ cultured for HSV isolation. Of the 41 patients, 34 had a definite history of herpetic keratitis, from 10 of whom (29.4%) HSV was isolated. There were no clinical features which distinguished between these groups; there was however an indication that those from whom HSV was not isolated had been previously treated with substantial amounts of topical acycloguanosine. In three patients of 12 patients when the disc was separated into 7 parts using a punch technique, virus was isolated exclusively from those portions demonstrating clinical scarring. Electron microscopy (EM) demonstrated HSV particles in stromal cells in the cultured corneas of seven patients. In two of the patients no virus was detected prior to culture with EM. In one patient HSV antigen was not found using peroxidase-antiperoxidase (PAP) staining prior to subsequently positive organ culture. Studies were made to determine how HSV accedes to the corneal stroma using a murine model in which keratitis occurs by zosteriform spread of HSV following inoculation of the snout. Preliminary evidence using PAP staining indicates that the virus reaches the stroma at the same time as the epithelium, via the sensory nerves. Evidence of HSV persistence in anterior segments was obtained in the same model, in contrast to which no virus could be isolated following direct inoculation into the cornea. It is speculated that for virus to set up a longterm association with the stromal keratocyte, it must be introduced via the sensory nerve.(ABSTRACT TRUNCATED AT 250 WORDS)