The role of IFN-gamma in immune responses to viral infections of the central nervous system.
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.
Chesler
David A
DA
Department of Biology, New York University, 1009 Main Building, 100 Washington Square East, New York, NY 10003, USA.
Reiss
Carol Shoshkes
CS
D000818:Animals; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015398:Signal Transduction
D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase