Department of Pathology, College of Veterinary Medicine, Athens, GA, 30602- 7388, USA.
Arch Virol. 2013 Nov;158(11):2297-305. doi: 10.1007/s00705-013-1743-2. Epub 2013 Jun 7.
Rabies virus (RABV) is a single-stranded, negative-sense RNA virus that causes a fatal neurological disease in humans and animals. Our previous studies have shown that lab-adapted, but not wild-type (wt), RABV enhances innate immune responses including type I interferon (IFN) and chemokines. To determine if treatment with type I IFN can inhibit RABV infection, mouse neuroblastoma and baby hamster kidney cells were treated with IFN-α before being infected with lab-adapted or wt RABV. It was found that lab-adapted, but not the wt, RABV was able to replicate in IFN-α-pretreated cells. To determine the genes in wt RABV that confer sensitivity to IFN-α treatment, the P and the glycoprotein (G) genes from the wt RABV were used to replace the respective genes in the lab-adapted RABV. The results revealed that it is the P, not the G, gene that is associated with IFN sensitivity. Further studies have identified the regions containing the self-association domain (residues 59-139) and the C-terminal (residue 175-297) region on the P that might be associated with IFN sensitivity. The expression of ISGs, such as ISG15, ISG56, PKR, OAS-1G, was also investigated and found to be greatly increased in wt, but not in lab-adapted RABV-infected cells. It is possible that the P protein from the lab-adapted RABV can interfere with the downstream events in the interferon-signaling cascade.
狂犬病病毒（RABV）是一种单链、负义 RNA 病毒，可导致人类和动物致命的神经系统疾病。我们之前的研究表明，实验室适应的但不是野生型（wt）RABV 增强了先天免疫反应，包括 I 型干扰素（IFN）和趋化因子。为了确定 I 型 IFN 的治疗是否可以抑制 RABV 感染，在用实验室适应的或 wt RABV 感染之前，用 IFN-α 处理小鼠神经母细胞瘤和幼仓鼠肾细胞。结果发现，实验室适应的，但不是 wt，RABV 能够在 IFN-α 预处理的细胞中复制。为了确定 wt RABV 中赋予对 IFN-α 治疗敏感性的基因，将 wt RABV 的 P 和糖蛋白（G）基因用于取代实验室适应的 RABV 中的相应基因。结果表明，与 IFN 敏感性相关的是 P 基因，而不是 G 基因。进一步的研究表明，P 中可能与 IFN 敏感性相关的区域包含自我缔合结构域（残基 59-139）和 C 末端（残基 175-297）区域。还研究了 ISG 的表达，如 ISG15、ISG56、PKR、OAS-1G，并发现 wt RABV 感染的细胞中其表达大大增加，而实验室适应的 RABV 感染的细胞中则没有。可能是实验室适应的 RABV 的 P 蛋白可以干扰干扰素信号转导级联的下游事件。
