Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Glia. 2011 Jan;59(1):58-67. doi: 10.1002/glia.21076. Epub 2010 Sep 27.
Herpes simplex virus Type I (HSV-1) is a neurotropic virus that is capable of infecting not only neurons, but also microglia and astrocytes and can establish latent infection in the central nervous system (CNS). We investigated whether IFN lambda (IFN-λ), a newly identified member of IFN family, has the ability to inhibit HSV-1 infection of primary human astrocytes and neurons. Both astrocytes and neurons were found to be highly susceptible to HSV-1 infection. However, upon IFN-λ treatment, HSV-1 replication in both astrocytes and neurons was significantly suppressed, which was evidenced by the reduced expression of HSV-1 DNA and proteins. This IFN-λ-mediated action on HSV-1 could be partially neutralized by antibody to IFN-λ receptor. Investigation of the mechanisms showed that IFN-λ treatment of astrocytes and neurons resulted in the upregulation of endogenous IFN-α/β and several IFN-stimulated genes (ISGs). To block IFN-α/β receptor by a specific antibody could compromise the IFN-λ actions on HSV-1 inhibition and ISG induction. In addition, IFN-λ treatment induced the expression of IFN regulatory factors (IRFs) in astrocytes and neurons. Furthermore, IFN-λ treatment of astrocytes and neurons resulted in the suppression of suppressor of cytokine signaling 1 (SOCS-1), a key negative regulator of IFN pathway. These data suggest that IFN-λ possesses the anti-HSV-1 function by promoting Type I IFN-mediated innate antiviral immune response in the CNS cells.
单纯疱疹病毒 1 型（HSV-1）是一种嗜神经病毒，不仅能够感染神经元，还能够感染小胶质细胞和星形胶质细胞，并能在中枢神经系统（CNS）中建立潜伏感染。我们研究了新型干扰素家族成员干扰素 λ（IFN-λ）是否具有抑制人原代星形胶质细胞和神经元感染单纯疱疹病毒 1 的能力。结果发现星形胶质细胞和神经元都极易受到 HSV-1 的感染。然而，经 IFN-λ 处理后，星形胶质细胞和神经元中的 HSV-1 复制均受到明显抑制，这表现在 HSV-1 DNA 和蛋白的表达减少。这种 IFN-λ 对 HSV-1 的作用可以被针对 IFN-λ 受体的抗体部分中和。对机制的研究表明，IFN-λ 处理星形胶质细胞和神经元导致内源性 IFN-α/β 和几种 IFN 刺激基因（ISGs）的上调。用特异性抗体阻断 IFN-α/β 受体可损害 IFN-λ 对 HSV-1 抑制和 ISG 诱导的作用。此外，IFN-λ 处理诱导星形胶质细胞和神经元中干扰素调节因子（IRFs）的表达。此外，IFN-λ 处理星形胶质细胞和神经元导致细胞因子信号转导抑制因子 1（SOCS-1）的表达受到抑制，SOCS-1 是 IFN 通路的关键负调控因子。这些数据表明，IFN-λ 通过在 CNS 细胞中促进 I 型 IFN 介导的先天抗病毒免疫反应，具有抗 HSV-1 的功能。
