Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
Virology. 2018 Sep;522:13-18. doi: 10.1016/j.virol.2018.06.013. Epub 2018 Jul 4.
Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that, following primary infection (varicella), establishes latency in sensory, autonomic, sympathetic and parasympathetic neurons, where it remains until reactivation (zoster). VZV-specific cell-mediated immune responses maintain VZV latency; thus, immunosuppressed and elderly persons are at risk of reactivation and associated neurological diseases. However, the cytokines produced by the immune system that control VZV in neurons are largely unknown. Therefore, to better understand how the immune system may restrict VZV in neurons, we studied interleukin-6, tumor necrosis factor-alpha and type 1 interferons for their ability to inhibit VZV replication in human neurons in vitro. Our studies revealed that VZV transcription and viral spread were significantly reduced by interleukin-6 and type 1 interferons, and to a lesser extent by tumor necrosis factor-alpha. These findings will help in understanding how the innate immune system limits virus replication in neurons in vivo.
水痘带状疱疹病毒（VZV）是一种嗜神经α疱疹病毒，在初次感染（水痘）后，潜伏在感觉、自主、交感和副交感神经元中，直到重新激活（带状疱疹）。VZV 特异性细胞免疫反应维持 VZV 潜伏期；因此，免疫抑制和老年人有重新激活和相关神经疾病的风险。然而，控制神经元中 VZV 的免疫系统产生的细胞因子在很大程度上是未知的。因此，为了更好地了解免疫系统如何在神经元中限制 VZV，我们研究了白细胞介素 6、肿瘤坏死因子-α 和 I 型干扰素抑制体外人神经元中 VZV 复制的能力。我们的研究表明，白细胞介素 6 和 I 型干扰素显著降低了 VZV 的转录和病毒传播，而肿瘤坏死因子-α 的作用则较小。这些发现将有助于了解先天免疫系统如何在体内限制神经元中的病毒复制。
