Attenuation of Mengo virus through genetic engineering of the 5' noncoding poly(C) tract.

Abstract:

:The murine cardioviruses, such as the Mengo and encephalomyocarditis 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 micrograms live virus (10(11) 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.

journal_name

Nature

journal_title

Nature

authors

Duke GM,Osorio JE,Palmenberg AC

doi

10.1038/343474a0

subject

Has Abstract

pub_date

1990-02-01 00:00:00

pages

474-6

issue

6257

eissn

0028-0836

issn

1476-4687

journal_volume

343

pub_type

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