Schijns V E, Van der Neut R, Haagmans B L, Bar D R, Schellekens H, Horzinek M C
Department of Virology, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.
J Gen Virol. 1991 Apr;72 ( Pt 4):809-15. doi: 10.1099/0022-1317-72-4-809.
The individual and synergistic antiviral effects of cytokines released by infiltrating immune cells or by cells of the nervous system may play an important role in inhibiting virus spread during infections of the central nervous system (CNS). We examined the antiviral activity against the neurotropic pseudorabies virus (PRV) of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and combinations of these cytokines, as compared to that of IFN-beta, in rat nervous tissue cells. PRV replicated efficiently in all neural cell types tested, including neurons, astrocytes and oligodendrocytes. The inhibitory effects were determined by quantifying the inhibition of virus plaque formation, yields of infectious virus at various times after infection and synthesis of viral proteins. At a low m.o.i., IFN-gamma and IFN-beta inhibited viral plaque formation in all cell types; TNF-alpha was effective only in astrocytes but showed synergy with IFN-gamma. At a higher m.o.i., IFN-beta inhibited yields of infectious virus more effectively than IFN-gamma, whereas TNF-alpha had no effect on virus yields and was only marginally synergistic with the antiviral activity of IFN-gamma. The yield-reduction assays correlated well with cytokine-induced inhibition of viral protein synthesis. Our results show that both IFN-gamma and IFN-beta can induce a state of antiviral resistance in neural cells whereas TNF-alpha is effective only in astrocytes at low m.o.i.; they suggest an antiviral role of cytokines in the immune response to virus infections of the CNS.
浸润免疫细胞或神经系统细胞释放的细胞因子的个体及协同抗病毒作用，可能在抑制中枢神经系统（CNS）感染期间病毒传播方面发挥重要作用。我们检测了干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）及其组合，与IFN-β相比，对大鼠神经组织细胞中嗜神经性伪狂犬病病毒（PRV）的抗病毒活性。PRV能在所有测试的神经细胞类型中高效复制，包括神经元、星形胶质细胞和少突胶质细胞。通过量化病毒空斑形成的抑制、感染后不同时间点感染性病毒的产量以及病毒蛋白的合成来确定抑制效果。在低感染复数（m.o.i.）时，IFN-γ和IFN-β在所有细胞类型中均抑制病毒空斑形成；TNF-α仅在星形胶质细胞中有效，但与IFN-γ表现出协同作用。在较高m.o.i.时，IFN-β比IFN-γ更有效地抑制感染性病毒产量，而TNF-α对病毒产量无影响，仅与IFN-γ的抗病毒活性有微弱协同作用。产量降低试验与细胞因子诱导的病毒蛋白合成抑制密切相关。我们的结果表明，IFN-γ和IFN-β均可在神经细胞中诱导抗病毒抗性状态，而TNF-α仅在低m.o.i.时对星形胶质细胞有效；它们提示细胞因子在对CNS病毒感染的免疫反应中具有抗病毒作用。
