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

Cytokine Growth Factor Rev. 2002 Dec;13(6):441-54. doi: 10.1016/s1359-6101(02)00044-8.


Interferon (IFN)-gamma, is not only a marker of T(H)1 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-gamma, 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-gamma in a fashion similar to peripheral fibroblasts or lymphocytes. We have illustrated this review with details about studies on the role(s) of IFN-gamma 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-gamma 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.

Publication types

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

MeSH terms

  • Animals
  • Central Nervous System / immunology*
  • Central Nervous System / virology*
  • Humans
  • Interferon-gamma / physiology*
  • Models, Biological
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Signal Transduction


  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase