A group B coxsackievirus/poliovirus 5 ' nontranslated region chimera can act as an attenuated vaccine strain in mice

The linear, single-stranded enterovirus RNA genome is flanked at either end with a nontranslated region (NTR), By replacing the entire 5' NTR of coxsa ckievirus B3 (CVB3) with that from type 1 poliovirus, a progeny virus was o btained following transfection of HeLa cells. The chimeric virus, CPV/49, r eplicates like the parental CVB3 strain in HeLa cells but is attenuated for replication and yield in primary human coronary artery endothelial cell cu ltures, in a human pancreas tumor cell line, and in primary murine heart fi broblast cultures. Western blotting analyses of CPV/49 replication in murin e heart fibroblast cultures demonstrate that synthesis of CPV/49 proteins i s significantly slower than that of the parental CVB3 strain. CPV/49 replic ates in murine hearts and pancreata, causing no disease in hearts and a min or pancreatic inflammation in some mice that resolves by 28 days postinocul ation. A single inoculation with CPV/49 induces protective anti-CVB3 neutra lizing antibody titers that completely protect mice from both heart and pan creatic disease when mice are challenged 28 days p.i. with genetically dive rse virulent strains of CVB3. That a chimeric CVB3 strain, created from seq uences of two virulent viruses, is sufficiently attenuated to act as an avi rulent, protective vaccine strain in mice suggests that chimeric genome tec hnology merits further evaluation for the development of new nonpoliovirus enteroviral vectors.