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protects mice from herpes simplex virus type 1 corneal disease
>
1 Department of Ophthalmology
and2 Department of Microbiology and Immunology, University of Illinois at Chicago College of Medicine, Chicago, Illinois 60612
3 Department of Microbiology and Immunology, Unit of Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan 48109
and4 Departments of Microbiology and Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, U.S.A.
Intravenous (i.v.) injection of u.v. light-inactivated herpes simplex virus type 1 (UV HSV-1) at the time of HSV-1 corneal infection reduced the cytotoxic T lymphocyte (CTL) response to HSV-1, and significantly reduced the incidence of HSV-1-induced corneal stromal disease in A/J mice. The spread of HSV-1 through the eye after corneal infection, detected using engineered HSV-1 (US3::Tn5-lacZ) with the lacZ gene under the transcriptional control of the viral late gene promoter for glycoprotein C, was also markedly reduced by i.v. UV HSV-1 injection. The restriction of HSV-1 corneal invasiveness in i.v. UV HSV-1-injected mice preceded the onset of a detectable specific cell-mediated or humoral immune response to HSV-1, and was accompanied by an elevated serum titre of interferon (IFN-
), reversed by anti-IFN-/
antibody, and mimicked by systemic IFN- treatment. IFN--treated mice developed a normal CTL response to HSV-1 after corneal infection, but the corneal invasiveness of the virus was markedly reduced and none of the treated mice developed corneal stromal disease. Together with our previous findings that HSV-1-specific CTLs participate in the pathogenesis of corneal stromal disease, these results indicate that i.v. injection of UV HSV-1 at the time of corneal infection may prevent stromal disease by the combined effects of IFN-mediated reduction of the spread of virus in the cornea and inhibition of the activity of the HSV-specific T lymphocytes that induce tissue destruction in the corneal stroma.
Present address: Department of Microbiology and Immunology, Pennsylvania State College of Medicine, Milton Hershey Medical Center, University Park, Pennsylvania 16802, U.S.A.
> Present address: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, U.S.A.
Received 2 January 1991;
accepted 28 March 1991.
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