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Published on: December 18, 2012
Immunopathological basis of lymphocytic choriomeningitis virus-induced chorioretinitis and keratitis
Martin S Zinkernagel1, Beatrice Bolinger, Philippe Krebs
1Research Department, Kantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland.
Abstract:
The infection of humans with the rodent-borne lymphocytic choriomeningitis virus (LCMV) can lead to central nervous system disease in adults or severe neurological disease with hydrocephalus and chorioretinitis in children infected congenitally. Although LCMV-induced meningitis and encephalitis have been studied extensively, the immunopathological mechanisms underlying LCMV infection-associated ocular disease remain elusive. We report here that the intraocular administration of the neurotropic LCMV strain Armstrong (Arm) elicited pronounced chorioretinitis and keratitis and that infection with the more viscerotropic strains WE and Docile precipitated less severe immunopathological ocular disease. Time course analyses revealed that LCMV Arm infection of the uvea and neuroretina led to monophasic chorioretinitis which peaked between days 7 and 12 after infection. Analyses of T-cell-deficient mouse strains showed that LCMV-mediated ocular disease was strictly dependent on the presence of virus-specific CD8(+) T cells and that the contribution of CD4(+) T cells was negligible. Whereas the topical application of immunosuppressive agents did not prevent the development of chorioretinitis, passive immunization with hyperimmune sera partially prevented retinal and corneal damage. Likewise, mice displaying preexisting LCMV-specific T-cell responses were protected against LCMV-induced ocular disease. Thus, antibody- and/or T-cell-based vaccination protocols could be employed as preventive strategies against LCMV-mediated chorioretinitis.
Insights
Lymphocytic choriomeningitis virus (LCMV) causes ocular disease, primarily chorioretinitis, dependent on CD8(+) T cells. Preventive vaccination strategies targeting antibodies and T cells show promise against LCMV-induced eye infections.
Area of Science:
- Immunology
- Virology
- Ophthalmology
Background:
- Lymphocytic choriomeningitis virus (LCMV) infection can cause central nervous system disease.
- LCMV-associated ocular disease, including chorioretinitis and keratitis, is not well understood.
- The immunopathological mechanisms of LCMV-induced eye disease require further investigation.
Purpose of the Study:
- To investigate the immunopathological mechanisms of LCMV-induced ocular disease.
- To determine the role of different LCMV strains in causing eye pathology.
- To evaluate potential preventive strategies against LCMV-mediated ocular disease.
Main Methods:
- Intraocular administration of LCMV strains (Armstrong, WE, Docile) in mice.
- Time course analysis of ocular inflammation.
- Assessment of LCMV-mediated ocular disease in T-cell-deficient mouse models.
- Evaluation of topical immunosuppressive agents and passive immunization.
- Analysis of pre-existing T-cell responses for protection.
Main Results:
- Neurotropic LCMV strain Armstrong induced severe chorioretinitis and keratitis.
- Viscerotropic strains WE and Docile caused less severe ocular disease.
- LCMV-induced ocular disease was dependent on virus-specific CD8(+) T cells, with minimal CD4(+) T cell involvement.
- Passive immunization and pre-existing T-cell immunity partially protected against ocular damage.
Conclusions:
- LCMV-mediated ocular disease pathogenesis is primarily driven by CD8(+) T cells.
- Antibody- and T-cell-based vaccination strategies may prevent LCMV-induced chorioretinitis.
- Further research into LCMV-specific immune responses can inform therapeutic and prophylactic approaches.
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