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Journal of Virology, May 2000, p. 4047-4056, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Group B Coxsackievirus/Poliovirus 5' Nontranslated Region Chimera Can Act as an Attenuated Vaccine Strain in Mice

Nora M. Chapman,1,* Anna Ragland,1,2 J. Smith Leser,1 Katja Höfling,1 Sandra Willian,1 Bert L. Semler,3 and Steven Tracy1

Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-64951; Department of Animal Science, University of Arizona, Tucson, Arizona 857212; and Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California 92697-40253

Received 30 June 1999/Accepted 21 January 2000

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.

* Corresponding author. Mailing address: Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198-6495. Phone: (402) 559-7747. Fax: (402) 559-4077. E-mail: nchapman{at}unmc.edu.

Journal of Virology, May 2000, p. 4047-4056, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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Copyright © 2000 by the American Society for Microbiology. All rights reserved.