Abstract
THE murine cardioviruses, such as the Mengo and encephalo-myocarditis viruses, and the bovine aphthoviruses, such as foot-and-mouth disease virus, are distinguished among positive-strand RNA viruses by the presence of long homopolymeric poly(C) tracts within their 5′ noncoding sequences. Although the specific lengths (60–350 bases) and sequence discontinuities (for example, uridine residues) that sometimes disrupt the homopolymer have served to characterize natural viral isolates, the biological function of the poly(C) region has never been clear. We now report that complementary DNA-mediated truncation of the Mengo virus poly(C) tract dramatically attenuates the pathogenicity of the virus in mice. Animals injected with viruses with short tracts not only survived inoculation of up to 50 μg live virus (1011 plaque-forming units) but consistently produced high titres of neutralizing antibodies, which conferred long-term immunogenic protection from (normally) lethal virus challenge. We propose that analogous synthetic strains of foot and mouth disease virus could serve as the basis for new attenuated vaccines.
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References
Duke, G. M. & Palmenberg, A. C. J. Virol. 63, 1822–1826 (1989).
Guthke, R., Ckenstedt, A. V., Güttner, J., Stracke, R. & Bergter, F. Acta. Virol. 31, 307–320 (1988).
Veckenstedt, A. Acta. Virol. 18, 501–507 (1974).
La Monica, N. & Racaniello, V. R. J. Virol. 63, 2357–2360 (1989).
Pilipenko, E. V., Blinov, V. M., Chernov, B. K., Dmitrieva, T. M. & Agol, V. I. Nucleic Acids Res. 17, 5701–5711 (1989).
Pilipenko, E. V. et al. Virology 168, 201–209 (1989).
Harris, T. J. R. & Brown, F. J. gen. Virol. 34, 87–105 (1977).
Costa Giomi, M. P. et al. Virology 162, 58–64 (1988).
Rueckert, R. R. & Wimmer, E. J. Virol. 50, 957–959 (1984).
Reed, L. J. & Muench, H. A. Am. J. Hyg. 27, 493–497 (1938).
Sherry, B. & Rueckert, R. R. J. Virol. 53, 137–143 (1985).
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Duke, G., Osorio, J. & Palmenberg, A. Attenuation of Mengo virus through genetic engineering of the 5′ noncoding poly(C) tract. Nature 343, 474–476 (1990). https://doi.org/10.1038/343474a0
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DOI: https://doi.org/10.1038/343474a0
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