A group B coxsackievirus/poliovirus 5′ nontranslated region chimera can act as an attenuated vaccine strain in mice
A group B coxsackievirus/poliovirus 5′ nontranslated region chimera can act as an attenuated vaccine strain in mice
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DOI：
10.1128/jvi.74.9.4047-4056.2000
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发表时间：
2000-05-01
影响因子：
5.4
通讯作者：
Tracy, S
中科院分区：
文献类型：
--
作者：
Chapman, NM;Ragland, A;Tracy, S
肠道病毒基因组为线性单链RNA，两端各有一个非翻译区（NTR）。将柯萨奇病毒B3（CVB 3）的5'端NTR全部替换为脊髓灰质炎1型病毒的NTR，转染HeLa细胞后获得子代病毒。嵌合病毒CPV/49在HeLa细胞中的复制与亲本CVB 3株相似，但在原代人冠状动脉内皮细胞培养物、人胰腺肿瘤细胞系和原代鼠心脏成纤维细胞培养物中的复制和产量减弱。CPV/49在小鼠心脏成纤维细胞培养物中复制的Western印迹分析表明CPV/49蛋白的合成比亲本CVB 3株的合成明显慢。CPV/49在小鼠心脏和胰腺中复制，在心脏中不引起疾病，在一些小鼠中引起轻微的胰腺炎症，该炎症在接种后28天消退。用CPV/49单次接种诱导保护性抗CVB 3中和抗体滴度，当小鼠感染后28天时，其完全保护小鼠免于心脏和胰腺疾病。基因多样的CVB 3病毒株嵌合CVB 3株，从两个强毒病毒的序列，是足够的减毒，作为一个无毒的，保护性疫苗株在小鼠中表明，嵌合基因组技术值得进一步评估新的非脊髓灰质炎病毒肠道病毒载体的发展。
The linear, single-stranded enterovirus RNA genome is flanked at either end with a nontranslated region (NTR), By replacing the entire 5' NTR of coxsackievirus B3 (CVB3) with that from type 1 poliovirus, a progeny virus was obtained following transfection of HeLa cells. The chimeric virus, CPV/49, replicates like the parental CVB3 strain in HeLa cells but is attenuated for replication and yield in primary human coronary artery endothelial cell cultures, in a human pancreas tumor cell line, and in primary murine heart fibroblast cultures. Western blotting analyses of CPV/49 replication in murine heart fibroblast cultures demonstrate that synthesis of CPV/49 proteins is significantly slower than that of the parental CVB3 strain. CPV/49 replicates in murine hearts and pancreata, causing no disease in hearts and a minor pancreatic inflammation in some mice that resolves by 28 days postinoculation. A single inoculation with CPV/49 induces protective anti-CVB3 neutralizing antibody titers that completely protect mice from both heart and pancreatic disease when mice are challenged 28 days p.i. with genetically diverse virulent strains of CVB3. That a chimeric CVB3 strain, created from sequences of two virulent viruses, is sufficiently attenuated to act as an avirulent, protective vaccine strain in mice suggests that chimeric genome technology merits further evaluation for the development of new nonpoliovirus enteroviral vectors.