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.
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Studies with Mengo virus in murine hosts suggest that the poly(C) length may play an important role in viral pathogenesis.
“Studies with Mengo virus in murine hosts suggest that the poly(C) length may play an important role in viral pathogenesis13”
From The encephalomyocarditis virus (2012) · cites this paper as [13]
Diminution of the length of the Mengovirus poly(C) strikingly attenuated its virulence, rendering it non-pathogenic in mice.
“It has been clearly demonstrated that diminution of the length of the Mengovirus poly(C) strikingly attenuated its virulence, rendering it non-pathogenic in mice.13,141”
From The encephalomyocarditis virus (2012) · cites this paper as [13]
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- Authors
- Duke, G. M., Osorio, J. E., & Palmenberg, A. C.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Nature
- Published
- 1990-02
- Volume
- 343
- Issue
- 6257
- Pages
- 474-476
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1975491920
- Cited by
- 163
- References
- 11
- Citations by year
- 2025: 3 · 2024: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 9 · 2013: 3 · 2012: 4
- FWCI
- 21.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Life Sciences › Agricultural and Biological Sciences › Agronomy and Crop Science › Animal Disease Management and Epidemiology
- Keywords
- mengovirus, poly(C) tract, 5' untranslated region, live attenuated vaccine, foot-and-mouth disease virus, encephalomyocarditis virus, neutralizing antibodies, positive-strand RNA viruses
- MeSH terms
- Animals, Antibodies, Viral, Antigens, Viral, Cloning, Molecular, DNA, Enterovirus Infections, Genes, Viral, Genetic Engineering, Mengovirus, Meningoencephalitis, Poly C, Polyribonucleotides, Mice
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