Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
Cell Microbiol. 2010 Mar;12(3):310-7. doi: 10.1111/j.1462-5822.2009.01395.x. Epub 2009 Oct 27.
Picornaviruses encompass a large family of RNA viruses. Some picornaviruses possess a leader (L) protein at the N-terminus of their polyprotein. The L proteins of encephalomyocarditis virus, a cardiovirus, and foot-and-mouth disease virus (FMDV), an aphthovirus, are both dispensable for replication and their major function seems to be the suppression of antiviral host cell responses. Previously, we showed that the L protein of mengovirus, a strain of encephalomyocarditis virus, inhibits antiviral responses by inhibiting type I interferon (IFN-alpha/beta) gene transcription. The L protein of the FMDV is a protease (L(pro)) that cleaves cellular factors to reduce cytokine and chemokine mRNA production and to inhibit cap-dependent cellular host mRNA translation, thereby limiting the production of proteins with antiviral activity. In this study, we constructed a viable chimeric mengovirus that expresses FMDV L(pro) in place of the authentic L protein in order to compare the efficiency of the immune evasion mechanisms mediated by L and L(pro) respectively. We show that in this mengovirus background the L protein is more potent than FMDV L(pro) in suppressing IFN-alpha/beta responses. Yet, FMDV L(pro) is important to antagonize infection-limiting responses both in vitro and in vivo.
小核糖核酸病毒包含一个大型的 RNA 病毒家族。一些小核糖核酸病毒在其多蛋白的 N 末端具有一个前导（L）蛋白。心脏口蹄疫病毒（一种口疮病毒）和口蹄疫病毒（一种口疮病毒）的 L 蛋白对于复制都是可有可无的，它们的主要功能似乎是抑制抗病毒的宿主细胞反应。以前，我们表明，脑心肌炎病毒（一种脑心肌炎病毒）的 L 蛋白通过抑制 I 型干扰素（IFN-α/β）基因转录来抑制抗病毒反应。口蹄疫病毒的 L 蛋白是一种蛋白酶（L（pro）），它可以切割细胞因子，减少细胞因子和趋化因子 mRNA 的产生，并抑制帽依赖性细胞宿主 mRNA 的翻译，从而限制具有抗病毒活性的蛋白质的产生。在这项研究中，我们构建了一种有活力的嵌合脑心肌炎病毒，它在表达 FMDV L（pro）的同时取代了真实 L 蛋白，以便比较分别由 L 和 L（pro）介导的免疫逃避机制的效率。我们表明，在这种脑心肌炎病毒背景下，L 蛋白比 FMDV L（pro）更能抑制 IFN-α/β 反应。然而，FMDV L（pro）对于在体外和体内拮抗感染限制反应都是很重要的。
