Bakhshesh Mehran, Groppelli Elisabetta, Willcocks Margaret M, Royall Elizabeth, Belsham Graham J, Roberts Lisa O
Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.
J Virol. 2008 Feb;82(4):1993-2003. doi: 10.1128/JVI.01957-07. Epub 2007 Dec 12.
Avian encephalomyelitis virus (AEV) is a picornavirus that causes disease in poultry worldwide, and flocks must be vaccinated for protection. AEV is currently classified within the hepatovirus genus, since its proteins are most closely related to those of hepatitis A virus (HAV). We now provide evidence that the 494-nucleotide-long 5' untranslated region of the AEV genome contains an internal ribosome entry site (IRES) element that functions efficiently in vitro and in mammalian cells. Unlike the HAV IRES, the AEV IRES is relatively short and functions in the presence of cleaved eIF4G and it is also resistant to an inhibitor of eIF4A. These properties are reminiscent of the recently discovered class of IRES elements within certain other picornaviruses, such as porcine teschovirus 1 (PTV-1). Like the PTV-1 IRES, the AEV IRES shows significant similarity to the hepatitis C virus (HCV) IRES in sequence, function, and predicted secondary structure. Furthermore, mutational analysis of the predicted pseudoknot structure at the 3' end of the AEV IRES lends support to the secondary structure we present. AEV is therefore another example of a picornavirus harboring an HCV-like IRES element within its genome, and thus, its classification within the hepatovirus genus may need to be reassessed in light of these findings.
禽脑脊髓炎病毒(AEV)是一种小RNA病毒,可在全球范围内引起家禽发病,因此禽群必须接种疫苗以进行预防。AEV目前被归类于肝病毒属,因为其蛋白质与甲型肝炎病毒(HAV)的蛋白质关系最为密切。我们现在提供证据表明,AEV基因组494个核苷酸长的5'非翻译区包含一个内部核糖体进入位点(IRES)元件,该元件在体外和哺乳动物细胞中均能高效发挥作用。与HAV IRES不同,AEV IRES相对较短,在eIF4G被切割的情况下仍能发挥作用,并且它对eIF4A的抑制剂也具有抗性。这些特性让人联想到最近在某些其他小RNA病毒(如猪捷申病毒1型,PTV-1)中发现的一类IRES元件。与PTV-1 IRES一样,AEV IRES在序列、功能和预测的二级结构上与丙型肝炎病毒(HCV)IRES具有显著相似性。此外,对AEV IRES 3'端预测的假结结构进行的突变分析支持了我们提出的二级结构。因此,AEV是另一个在其基因组中含有类似HCV的IRES元件的小RNA病毒实例,因此,鉴于这些发现,可能需要重新评估其在肝病毒属中的分类。