Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8051, St. Louis, MO 63110, USA.
J Virol. 2011 Nov;85(22):11557-66. doi: 10.1128/JVI.05519-11. Epub 2011 Aug 31.
Type I interferon (IFN) signaling coordinates an early antiviral program in infected and uninfected cells by inducing IFN-stimulated genes (ISGs) that modulate viral entry, replication, and assembly. However, the specific antiviral functions in vivo of most ISGs remain unknown. Here, we examined the contribution of the ISG viperin to the control of West Nile virus (WNV) in genetically deficient cells and mice. While modest increases in levels of WNV replication were observed for primary viperin(-/-) macrophages and dendritic cells, no appreciable differences were detected in deficient embryonic cortical neurons or fibroblasts. In comparison, viperin(-/-) adult mice infected with WNV via the subcutaneous or intracranial route showed increased lethality and/or enhanced viral replication in central nervous system (CNS) tissues. In the CNS, viperin expression was induced in both WNV-infected and adjacent uninfected cells, including activated leukocytes at the site of infection. Our experiments suggest that viperin restricts the infection of WNV in a tissue- and cell-type-specific manner and may be an important ISG for controlling viral infections that cause CNS disease.
I 型干扰素 (IFN) 通过诱导干扰素刺激基因 (ISG) 来协调受感染和未受感染细胞中的早期抗病毒程序，这些基因可调节病毒进入、复制和组装。然而，大多数 ISG 在体内的具体抗病毒功能仍然未知。在这里，我们研究了 ISG viperin 对西尼罗河病毒 (WNV) 在基因缺陷细胞和小鼠中的控制作用。虽然在原代 viperin(-/-)巨噬细胞和树突状细胞中观察到 WNV 复制水平适度增加，但在缺陷的胚胎皮质神经元或成纤维细胞中未检测到明显差异。相比之下，通过皮下或颅内途径感染 WNV 的 viperin(-/-)成年小鼠表现出更高的致死率和/或中枢神经系统 (CNS) 组织中增强的病毒复制。在 CNS 中，WNV 感染和相邻未感染细胞均诱导了 viperin 的表达，包括感染部位的活化白细胞。我们的实验表明，viperin 以组织和细胞类型特异性的方式限制 WNV 的感染，并且可能是控制导致 CNS 疾病的病毒感染的重要 ISG。
