Lack of interferon-gamma produces encephalitis and increased apoptosis in transgenic mice infected with HSV-1

K. D. Geiger, W. Schlote, N. E. Sarvetnick

Research output: Contribution to journalArticle

Abstract

Purpose. To investigate the role of systemic interferon-gamma (IFN-γ) in intraocular and intraerebral infection with herpes simplex virus type 1 (HSV-1), we infected IFN-γ-deficient transgenic mice (GKO) intravitreally with HSV-1, strain F. Methods. The right eyes of GKO transgenic and nontransgenic mice were injected intravitreally with 2 × 105 pfu of HSV-1. Pathological changes were assessed by histology and immunocytochemistry using the indirect peroxidase method. Apoptosis in the brain was evaluated by morphology and by in situ labeling of 3′-OH DNA ends (TUNEL). Results. We found viral antigen in the eyes and in the brain of all infected animals by d6. The mice developed viral infection of both eyes, the optic nerve and the brain. GKO transgenic mice survived infection with HSV-1 although they developed encephalitis that receded by d12. Nontransgenic mice did not develop encephalitis. Neurological symptoms correlated with increased apoptosis of neurons in the brains of transgenic mice and downregulation of the protooncogene bcl-2. Inducible NO synthetase was scarcely influenced. Conclusions. Our observations confirm the importance of systemic interferon-gamma production for the generation of encephalitis in viral infection, and induction of apoptosis in neurons. Some of the cytokine's antiviral activities may rely on influencing factors preventing apoptosis or on changes of viral genome expression.

Original languageEnglish (US)
Pages (from-to)S952
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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