Drappier Melissa, Opperdoes Fred R, Michiels Thomas
Université Catholique de Louvain, de Duve Institute, Brussels, Belgium.
Université Catholique de Louvain, de Duve Institute, Brussels, Belgium
J Virol. 2017 Jun 26;91(14). doi: 10.1128/JVI.00573-17. Print 2017 Jul 15.
Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is of human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the nonstructural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. By using coimmunoprecipitation and functional RNase L assays, the species specificity of RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed the species specificity of L* activity and showed that L* from rat strain RTV-1 inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L* protein was phylogenetically related to L* of mouse viruses and that it failed to inhibit human RNase L but readily antagonized mouse RNase L, unambiguously showing the mouse origin of VHEV. Defining the natural host of a virus can be a thorny issue, especially when the virus was isolated only once or when the isolation story is complex. The species includes Theiler's murine encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus (VHEV), however, was isolated from mice that were inoculated with cerebrospinal fluid of a patient presenting with chronic encephalitis. It is therefore unclear whether VHEV was derived from the human sample or from the inoculated mouse. The L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate immunity, in a species-specific manner. Using binding and functional assays, we show that this species specificity even allows discrimination between TMEV strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse but not human RNase L, indicating that this virus originates from mice.
维柳伊斯克人脑炎病毒（VHEV）是一种与泰勒氏鼠脑脊髓炎病毒（TMEV）相关的小核糖核酸病毒。VHEV是从在小鼠体内传代的人体材料中分离出来的。因此，这种VHEV的起源是人类还是小鼠尚不清楚。我们利用泰勒病毒非结构L蛋白的种属特异性活性来追踪TMEV分离株的起源。TMEV L抑制核糖核酸酶L，即干扰素途径的效应酶。通过共免疫沉淀和功能性核糖核酸酶L测定，对来自小鼠（DA）和大鼠（RTV-1）TMEV株以及VHEV的L进行核糖核酸酶L拮抗作用的种属特异性测试。共免疫沉淀和功能测定数据证实了L活性的种属特异性，并表明来自大鼠株RTV-1的L抑制大鼠核糖核酸酶L，但不抑制小鼠或人类核糖核酸酶L。接下来，我们表明VHEV L蛋白在系统发育上与小鼠病毒的L相关，并且它不能抑制人类核糖核酸酶L，但能轻易拮抗小鼠核糖核酸酶L，明确显示VHEV起源于小鼠。确定病毒的天然宿主可能是一个棘手的问题，特别是当该病毒仅被分离过一次或分离情况复杂时。该种属包括感染小鼠和大鼠的泰勒氏鼠脑脊髓炎病毒（TMEV）以及感染人类的萨福尔德病毒（SAFV）。然而，一种TMEV株，即维柳伊斯克人脑炎病毒（VHEV），是从接种了一名患有慢性脑炎患者脑脊液的小鼠中分离出来的。因此，尚不清楚VHEV是源自人类样本还是接种的小鼠。TMEV编码的L蛋白以种属特异性方式抑制核糖核酸酶L，这是一种参与先天免疫的细胞酶。通过结合和功能测定，我们表明这种种属特异性甚至能够区分小鼠和大鼠来源的TMEV株。VHEV L*蛋白明显抑制小鼠核糖核酸酶L，但不抑制人类核糖核酸酶L，表明该病毒起源于小鼠。
