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Journal of Virology, January 2009, p. 159-166, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01211-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Immunopathological Basis of Lymphocytic Choriomeningitis Virus-Induced Chorioretinitis and Keratitis{triangledown}

Martin S. Zinkernagel,1,2 Beatrice Bolinger,2 Philippe Krebs,2 Lucas Onder,2 Simone Miller,2 and Burkhard Ludewig2*

Clinic of Ophthalmology,1 Research Department, Kantonal Hospital of St. Gallen, 9007 St. Gallen, Switzerland2

Received 11 June 2008/ Accepted 8 October 2008

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.

* Corresponding author. Mailing address: Research Department, Kantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland. Phone: 41 71 4941090. Fax: 41 71 4946321. E-mail: burkhard.ludewig{at}kssg.ch

{triangledown} Published ahead of print on 22 October 2008.

Journal of Virology, January 2009, p. 159-166, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01211-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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