Endogenously produced interferon alpha protects mice from herpes simplex virus type 1 corneal disease.
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-alpha), reversed by anti-IFN-alpha/beta antibody, and mimicked by systemic IFN-alpha treatment. IFN-alpha-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.
Hendricks
R L
RL
Department of Ophthalmology, University of Illinois, Chicago College of Medicine 60612.
Weber
P C
PC
Taylor
J L
JL
Koumbis
A
A
Tumpey
T M
TM
Glorioso
J C
JC
D000818:Animals; D002924:Ciliary Body / Q000382:microbiology; D003315:Cornea / Q000382:microbiology / Q000473:pathology; D004198:Disease Susceptibility; D005260:Female; D007370:Interferon Type I / Q000276:immunology*; D007498:Iris / Q000382:microbiology; D007635:Keratitis, Dendritic / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D012160:Retina / Q000382:microbiology; D018139:Simplexvirus / Q000276:immunology* / Q000502:physiology / Q000528:radiation effects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D012668:Trigeminal Ganglion / Q000382:microbiology; D014466:Ultraviolet Rays
D007370:Interferon Type I