Institute of Virology, Vetmeduni Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
Sci Rep. 2017 Mar 14;7:44459. doi: 10.1038/srep44459.
A multitude of viral factors - either inhibiting the induction of the IFN-system or its effectors - have been described to date. However, little is known about the role of structural components of the incoming virus particle in protecting against IFN-induced antiviral factors during or immediately after entry. In this study, we take advantage of the previously reported property of Classical swine fever virus (family Flaviviridae, genus Pestivirus) to tolerate a deletion of the core protein if a compensatory mutation is present in the NS3-helicase-domain (Vp447). In contrast to the parental virus (Vp447), which causes a hemorrhagic-fever-like disease in pigs, Vp447 is avirulent in vivo. In comparison to Vp447, growth of Vp447 in primary porcine cells and IFN-treated porcine cell lines was reduced >20-fold. Also, primary porcine endothelial cells and IFN-pretreated porcine cell lines were 8-24 times less susceptible to Vp447. This reduction of susceptibility could be partially reversed by loading Vp447 particles with different levels of core protein. In contrast, expression of core protein in the recipient cell did not have any beneficial effect. Therefore, a protective effect of core protein in the incoming virus particle against the products of IFN-stimulated genes could be demonstrated.
迄今为止，已经描述了许多病毒因素-无论是抑制 IFN 系统的诱导还是其效应物-。然而，对于进入病毒颗粒的结构成分在进入或进入后立即抵抗 IFN 诱导的抗病毒因子的作用知之甚少。在这项研究中，我们利用先前报道的经典猪瘟病毒（黄病毒科，瘟病毒属）的特性，如果 NS3 解旋酶结构域（Vp447）中存在补偿性突变，则可以耐受核心蛋白的缺失。与引起猪出血热样疾病的亲本病毒（Vp447）相比，Vp447 在体内无毒。与 Vp447 相比，Vp447 在原代猪细胞和 IFN 处理的猪细胞系中的生长减少了> 20 倍。此外，原代猪内皮细胞和 IFN 预处理的猪细胞系对 Vp447 的敏感性降低了 8-24 倍。通过用不同水平的核心蛋白装载 Vp447 颗粒，可以部分逆转这种敏感性降低。相比之下，在受者细胞中表达核心蛋白没有任何有益作用。因此，可以证明进入病毒颗粒的核心蛋白对 IFN 刺激基因产物具有保护作用。
