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Updated: Aug 8, 2026
Ex Vivo Organotypic Corneal Model of Acute Epithelial Herpes Simplex Virus Type I Infection
Published on: November 3, 2012
Ocular infection with herpes simplex virus in several strains of rat
S M Nicholls1, A Benylles, C Shimeld
1Department of Ophthalmology, School of Medical Sciences, Bristol Eye Hospital, United Kingdom.
Purpose:
To assess the suitability of the rat for studies of ocular infection with herpes simplex virus (HSV).
Methods:
LEW, AO, DA, PVG, and (DAxLEW)F1 x LEW backcross generation rats, 7 to 9 weeks of age, were inoculated with HSV-1 McKrae. The course of primary disease was assessed by clinical observation using a slit lamp. Infectious virus was assayed in ocular and nervous tissue, and the incidence of latent infection was determined.
Results:
LEW and AO strains were the most susceptible. All LEW rats died after an inoculum of 4 x 10(2) plaque-forming units (pfu) and developed severe corneal disease and uveitis. In contrast, all PVG rats survived 10(4) pfu, 60% survived 4 x 10(4) pfu, and eye disease was restricted to epithelial lesions, sometimes accompanied by mild stromal haze. This resolved, even in animals that developed central nervous system disease. The DA strain showed intermediate susceptibility. Resistance was dominant because disease in backcross generation (DA x LEW)F1 x LEW rats resembled that of the DA rather than the LEW strain. Resistance appeared to be linked to coat color (P < 0.001) rather than to major histocompatibility complex (MHC) type. Chronic stromal disease did not occur in survivors (DA, PVG, and hybrid strains only).
Conclusions:
The susceptibility of rat strains to infection of the cornea with HSV varies, and, as with mice, resistance seems to be controlled by non-MHC genes. Rats may prove useful for immunologic studies. Virus reactivation will be the subject of a future report.
Insights
Rat strain susceptibility to herpes simplex virus (HSV) ocular infection varies significantly. Resistance to HSV eye disease in rats appears controlled by non-MHC genes, suggesting their utility in immunological studies.
Area of Science:
- Ophthalmology
- Virology
- Immunology
Background:
- Herpes simplex virus (HSV) ocular infections are a significant cause of vision loss.
- Animal models are crucial for understanding HSV pathogenesis and developing therapies.
- The rat model's suitability for HSV ocular infection studies requires further characterization.
Purpose of the Study:
- To evaluate the susceptibility of different rat strains to ocular herpes simplex virus (HSV) infection.
- To determine the genetic basis of resistance and susceptibility to HSV keratitis in rats.
- To assess the potential of rats as a model for HSV ocular disease research.
Main Methods:
- Inoculation of five rat strains (LEW, AO, DA, PVG, and (DAxLEW)F1 x LEW backcross) with HSV-1 McKrae.
- Clinical assessment of ocular disease using slit lamp examination.
- Quantification of infectious virus in ocular and nervous tissues and determination of latent infection incidence.
Main Results:
- LEW and AO rat strains exhibited high susceptibility, with high mortality and severe corneal disease and uveitis.
- PVG rats demonstrated significant resistance, with survival at high inoculums and limited epithelial lesions.
- Resistance was dominant in backcross generations and appeared linked to coat color, not MHC type, with no chronic stromal disease in resistant strains.
Conclusions:
- Rat strain susceptibility to HSV ocular infection is variable.
- Resistance to HSV eye infection in rats is likely controlled by non-MHC genes, similar to mice.
- Rats may serve as a valuable model for immunological investigations of HSV ocular infections.
