Chesler David A, Reiss Carol Shoshkes
Department of Biology, New York University, 1009 Main Building, 100 Washington Square East, New York, NY 10003, USA.
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.
干扰素（IFN）-γ不仅是辅助性T细胞1（TH1）、CD4、CD8和自然杀伤（NK）细胞的标志物，还是一种关键的抗病毒介质，对于从中枢神经系统清除病毒至关重要。在本综述中，我们描述了IFN-γ、其受体、受体结合后的信号转导以及抗病毒下游介质。我们证明，尽管神经元是终末分化且不可更新的，但它们对IFN-γ的反应方式与外周成纤维细胞或淋巴细胞相似。我们通过关于IFN-γ在麻疹病毒（MV）、单纯疱疹病毒1型（HSV-1）和水疱性口炎病毒（VSV）中枢神经系统感染发病机制中作用的研究细节来说明本综述。对于VSV感染，IFN-γ通过Jaks 1和2以及信号转导和转录激活因子1（STAT1）发出信号，以激活干扰素调节因子（IRF）-1；尽管病毒蛋白合成受到抑制，但蛋白激酶R（PKR）在小鼠神经元对VSV的抗病毒反应中并非关键介质。相反，1型一氧化氮合酶（NOS）的诱导及其产生的一氧化氮对于从神经元中清除病毒至关重要。
