Interferon lambda inhibits herpes simplex virus type I infection of human astrocytes and neurons.
Interferon lambda inhibits herpes simplex virus type I infection of human astrocytes and neurons.
复制标题
作者：
Li, Jieliang;Hu, Shuxian;Zhou, Lin;Ye, Li;Wang, Xu;Ho, Jie;Ho, Wenzhe
单纯疱疹病毒I型（HSV-1）是一种嗜神经病毒，其不仅能够感染神经元，而且能够感染小胶质细胞和星形胶质细胞，并且可以在中枢神经系统（CNS）中建立潜伏感染。我们研究了IFN-λ（IFN-λ）作为IFN家族的新成员是否具有抑制HSV-1感染原代人星形胶质细胞和神经元的能力。发现星形胶质细胞和神经元对HSV-1感染高度敏感。然而，在IFN-λ处理后，星形胶质细胞和神经元中的HSV-1复制均被显著抑制，这通过HSV-1 DNA和蛋白质的表达减少来证明。IFN-λ介导的抗HSV-1作用可被IFN-λ受体抗体部分中和。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（ISG）的上调。用特异性抗体阻断IFN-α/β受体可减弱IFN-λ抑制HSV-1和诱导ISG的作用。此外，IFN-λ处理诱导星形胶质细胞和神经元中IFN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）的抑制，SOCS-1是IFN途径的关键负调节因子。提示IFN-λ通过促进I型IFN介导的CNS细胞天然抗病毒免疫应答而具有抗HSV-1的作用。
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.
登录
查看更多内容
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
6
作者：
Ank, Nina;Paludan, Soren R.
通讯作者：
Paludan, Soren R.
影响因子：
5.4
作者：
Mikloska, Z;Cunningham, AL
通讯作者：
Cunningham, AL
λ干扰素抑制人类免疫缺陷病毒1型巨噬细胞感染
影响因子：
5.4
作者：
Hou, Wei;Wang, Xu;Ho, Wen-Zhe
通讯作者：
Ho, Wen-Zhe
DOI：
10.1073/pnas.0308057100
发表时间：
2004-02-03
影响因子：
11.1
作者：
Kurt-Jones, EA;Chan, M;Finberg, RW
通讯作者：
Finberg, RW