Cytokine-mediated survival from lethal herpes simplex virus infection: Role of programmed neuronal death

Kathrin D. Geiger, Deepak Gurushanthaiah, Edward L. Howes, Gail A. Lewandowski, John C. Reed, Floyd E. Bloom, Nora E. Sarvetnick

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The mechanisms responsible for cytokine-mediated antiviral effects are not fully understood. We approached this problem by studying the outcome of intraocular herpes simplex (HSV) infection in transgenic mice that express interferon γ in the photoreceptor cells of the retina. These transgenic mice showed selective survival from lethal HSV-2 infection manifested in both eyes, the optic nerve, and the brain. Although transgenic mice developed greater inflammatory responses to the virus in the eyes, inflammation and viral titers in their brains were equivalent to nontransgenic mice. However, survival of transgenic mice correlated with markedly lower numbers of central neurons undergoing apoptosis. The protooncogene Bc12 was found to be induced in the HSV-2-infected brains of transgenic mice, allowing us to speculate on its role in fostering neuronal survival in this model. These observations imply a complex interaction between cytokine, virus, and host cellular factors. Our results suggest a cytokine-regulated salvage pathway that allows for survival of infected neurons.

Original languageEnglish (US)
Pages (from-to)3411-3415
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number8
DOIs
StatePublished - Apr 11 1995

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Virus Diseases
Simplexvirus
Transgenic Mice
Cytokines
Human Herpesvirus 2
Brain
Viruses
Neurons
Photoreceptor Cells
Herpes Simplex
Foster Home Care
Optic Nerve
Infection
Interferons
Antiviral Agents
Retina
Apoptosis
Inflammation

Keywords

  • Bcl2
  • apoptosis
  • interferon γ
  • transgenic mice

ASJC Scopus subject areas

  • General

Cite this

Cytokine-mediated survival from lethal herpes simplex virus infection : Role of programmed neuronal death. / Geiger, Kathrin D.; Gurushanthaiah, Deepak; Howes, Edward L.; Lewandowski, Gail A.; Reed, John C.; Bloom, Floyd E.; Sarvetnick, Nora E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 8, 11.04.1995, p. 3411-3415.

Research output: Contribution to journalArticle

Geiger, Kathrin D. ; Gurushanthaiah, Deepak ; Howes, Edward L. ; Lewandowski, Gail A. ; Reed, John C. ; Bloom, Floyd E. ; Sarvetnick, Nora E. / Cytokine-mediated survival from lethal herpes simplex virus infection : Role of programmed neuronal death. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 8. pp. 3411-3415.
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