Endogenously produced interferon alpha protects mice from herpes simplex virus type 1 corneal disease

J Gen Virol. 1991 Jul;72 ( Pt 7):1601-10. doi: 10.1099/0022-1317-72-7-1601.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ciliary Body / microbiology
  • Cornea / microbiology
  • Cornea / pathology
  • Disease Susceptibility
  • Female
  • Interferon Type I / immunology*
  • Iris / microbiology
  • Keratitis, Dendritic / immunology*
  • Keratitis, Dendritic / pathology
  • Mice
  • Mice, Inbred A
  • Retina / microbiology
  • Simplexvirus / immunology*
  • Simplexvirus / physiology
  • Simplexvirus / radiation effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • Trigeminal Ganglion / microbiology
  • Ultraviolet Rays

Substances

  • Interferon Type I