The stem loop II within the 5′ nontranslated region of clinical coxsackievirus B3 genomes determines cardiovirulence phenotype in a murine model
The stem loop II within the 5′ nontranslated region of clinical coxsackievirus B3 genomes determines cardiovirulence phenotype in a murine model
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DOI：
10.1086/374877
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发表时间：
2003-05-15
影响因子：
6.4
通讯作者：
Romero, JR
中科院分区：
文献类型：
--
作者：
Dunn, JJ;Bradrick, SS;Romero, JR
柯萨奇病毒B3（CVB3）是引起人类急性心肌炎的主要病毒，并与扩张型心肌病的发病机制有关。其他文献已经证明，对于2个野生型CVB3毒株，心脏毒力表型的主要分子决定因子定位于5'非翻译区（5' NTR）。在本研究中，通过构建CVB 3嵌合体，预测的5' NTR内的茎环（SL）II已被鉴定为心脏毒力的主要病毒决定因素。在心脏来源的鼠成纤维细胞中的复制测定显示，只有心脏毒性株在37 ℃下生长健壮，而所有病毒株在HeLa细胞中有效复制。RNA二级结构的计算分析表明，预测的SLII的noncardiotriculate分离显着不同的心肌菌株。这些结果表明，对于临床CVB3分离株，心脏毒力的主要决定因素定位于预测的SLII。这种高阶RNA结构的特性可能是心肌细胞生产性感染所必需的。
Coxsackievirus B3 (CVB3) is a principal viral cause of acute myocarditis in humans and has been implicated in the pathogenesis of dilated cardiomyopathy. It has been demonstrated elsewhere that, for 2 wild-type CVB3 strains, the primary molecular determinant of cardiovirulence phenotype localizes to the 5' nontranslated region (5' NTR). Here in this study, through construction of CVB3 chimeras, the predicted stem loop (SL) II within the 5' NTR has been identified as a primary viral determinant of cardiovirulence. Replication assays in cardiac-derived murine fibroblasts revealed that only cardiovirulent strains grow robustly at 37 degreesC, whereas all virus strains replicate efficiently in HeLa cells. Computational analyses of RNA secondary structure suggest that the predicted SLII of the noncardiovirulent isolate differs significantly from that of myocarditic strains. These results indicate that, for clinical CVB3 isolates, the major determinant of cardiovirulence localizes to the predicted SLII. The identity of this higher-order RNA structure may be essential for productive infection of cardiac cells.