The role of IFN-γ in immune responses to viral infections of the central nervous system

David A. Chesler, Carol Shoshkes Reiss

Research output: Contribution to journalReview articlepeer-review

Abstract

Interferon (IFN)-γ, is not only a marker of TH1 CD4, CD8 and natural killer (NK) cells, it is also a critical antiviral mediator which is central to the elimination of viruses from the CNS. In this review, we describe IFN-γ, its receptor, signal transduction from receptor engagement, and antiviral downstream mediators. We demonstrate that although neurons are post-mitotic and non-renewing, they respond to IFN-γ in a fashion similar to peripheral fibroblasts or lymphocytes. We have illustrated this review with details about studies on the role(s) of IFN-γ in the pathogenesis of measles virus (MV), herpes simplex virus (HSV) type 1, and vesicular stomatitis virus (VSV) infections of the CNS. For VSV infection, IFN-γ signals through Jaks 1 and 2 and STAT1 to activate (interferon regulatory factor) IRF-1; although viral protein synthesis is inhibited, PKR is not a critical mediator in the antiviral response to VSV in murine neurons. In contrast, induction of nitric oxide synthase (NOS) type 1 and its production of nitric oxide is essential in the elimination of viruses from neurons.

Original languageEnglish (US)
Pages (from-to)441-454
Number of pages14
JournalCytokine and Growth Factor Reviews
Volume13
Issue number6
DOIs
StatePublished - Dec 2002

Keywords

  • Antiviral
  • Interferon-γ
  • Neuron
  • Nitric oxide
  • Virus

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Immunology
  • General Biochemistry, Genetics and Molecular Biology

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