ENTEROVIRUS 71 LEADER: TARGET FOR PEPTIDE INHIBITORS

描述每年有数十万儿童感染肠道病毒71（EV 71）。感染EV 71可导致严重并发症，如脊髓灰质炎样瘫痪、脑炎、脑膜炎甚至死亡。目前，没有针对EV 71的治疗方法或疫苗。EV 71属于小核糖核酸病毒家族，其成员含有正链RNA基因组，这些基因组通过内部核糖体进入的不寻常机制进行翻译。将利用大多数细胞和病毒mRNA的翻译起始模型之间的差异来鉴定可以选择性抑制EV 71 mRNA翻译的小肽。具体而言，表达构象约束肽文库的逆转录病毒将用于感染表达连接至增强型绿色荧光蛋白（EGFP）报告基因的EV 71 5'非编码区和连接至增强型黄色荧光蛋白（EYFP）的细胞c-myc 5'非编码区的细胞。通过细胞分选分离不能表达EGFP但仍表达EYFP的感染细胞，并分离编码推定抑制剂的基因。研究抑制肽的靶点并表征它们破坏的分子相互作用将揭示更多关于病毒如何发挥功能以招募宿主细胞分子进行翻译的信息。选择和表征的细胞内稳定的肽，可以抑制病毒RNA基因组的扩增应水平的新方法，在寻找抗病毒治疗。

DESCRIPTION Every year hundreds of thousands of children are infected with enterovirus 71 (EV71). Infection with EV71 can lead to serious complications such as polio-like paralysis, encephalitis, meningitis or even death. Currently, there is no treatment or vaccine against EV71. EV71 belongs to the picornavirus family, whose members contain positive-stranded RNA genomes that are translated by an unusual mechanism of internal ribosome entry. The differences between the model of translational initiation of most cellular and viral mRNAs will be exploited to identify small peptides that can selectively inhibit the translation of the EV71 mRNA. Specifically, retroviruses expressing conformationally constrained peptide libraries will be used to infect cells expressing the EV71 5' non-coding region linked to an enhanced green fluorescent protein (EGFP) reporter gene and a cellular c-myc 5' non- coding region linked to an enhanced yellow fluorescence protein (EYFP). Infected cells which fail to express EGFP but still express EYFP will be isolated by cell sorting, and the gene encoding the putative inhibitor will be isolated . Studying the targets of the inhibitory peptides and characterizing the molecular interactions that they are disrupting will reveal more about how viruses function to recruit host cell molecules for their translation. Selection and characterization of intracellularly stable peptides that can inhibit the amplification of a viral RNA genome should level to novel ways in the search for antiviral therapeutics.