Discipline of Infectious Diseases and Immunology, The University of Sydney, Sydney, Australia.
School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Perth, Australia.
J Gen Virol. 2011 Jun;92(Pt 6):1380-1390. doi: 10.1099/vir.0.029371-0. Epub 2011 Feb 23.
Enterovirus 71 (EV71) is a member of the species Human enterovirus A within the family Picornaviridae and is a major causative agent of epidemics of hand, foot and mouth disease associated with severe neurological disease. Three EV71 genogroups, designated A, B and C, have been identified, with 75-84 % nucleotide sequence similarity between them. Two strains, EV71-26M (genogroup B) and EV71-6F (genogroup C), were found to have distinct cell-culture growth (26M, rapid; 6F, slow) and plaque-formation (26M, large; 6F, small) phenotypes. To identify the genome regions responsible for the growth phenotypes of the two strains, a series of chimeric viruses was constructed by exchanging the 5' untranslated region (UTR), P1 structural protein or P2/P3 non-structural protein gene regions plus the 3'UTR using infectious cDNA clones of both virus strains. Analysis of reciprocal virus chimeras revealed that the 5'UTRs of both strains were compatible, but not responsible for the observed phenotypes. Introduction of the EV71-6F P1 region into the EV71-26M clone resulted in a small-plaque and slow-growth phenotype similar to that of EV71-6F, whereas the reciprocal chimera displayed intermediate-growth and intermediate-sized plaque phenotypes. Introduction of the EV71-26M P2-P3-3'UTR regions into the EV71-6F clone resulted in a large-plaque and rapid-growth phenotype identical to that of strain EV71-26M, whereas the reciprocal chimera retained the background strain large-plaque phenotype. These results indicate that, although both the P1 and P2-P3-3'UTR genome regions influence the EV71 growth phenotype in cell culture, phenotype expression is dependent on specific genome-segment combinations and is not reciprocal.
肠道病毒 71 型（EV71）是小核糖核酸病毒科肠道病毒属的人肠道病毒 A 种的一个成员，是导致与严重神经疾病相关的手足口病爆发的主要病原体。已经鉴定出三个 EV71 基因群，分别命名为 A、B 和 C，它们之间的核苷酸序列相似性为 75-84%。发现两种株系，EV71-26M（基因群 B）和 EV71-6F（基因群 C），具有明显不同的细胞培养生长（26M，快速；6F，缓慢）和蚀斑形成（26M，大；6F，小）表型。为了确定这两种株系的生长表型的基因组区域，使用两种病毒株的感染性 cDNA 克隆，通过交换 5'非翻译区（UTR）、P1 结构蛋白或 P2/P3 非结构蛋白基因区加上 3'UTR，构建了一系列嵌合病毒。对相互嵌合病毒的分析表明，两种株系的 5'UTR 是相容的，但不是造成观察到的表型的原因。将 EV71-6F 的 P1 区引入 EV71-26M 克隆中，导致类似 EV71-6F 的小蚀斑和生长缓慢表型，而反向嵌合病毒则表现出中等生长和中等大小蚀斑表型。将 EV71-26M 的 P2-P3-3'UTR 区引入 EV71-6F 克隆中，导致与 EV71-26M 株相同的大蚀斑和快速生长表型，而反向嵌合病毒则保留了背景株的大蚀斑表型。这些结果表明，尽管 P1 和 P2-P3-3'UTR 基因组区域都影响细胞培养中的 EV71 生长表型，但表型表达取决于特定的基因组片段组合，并且不是相互的。
