Journal ArticleDOI
Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates.
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To the best of the knowledge, this is the first report of a specific nutritional deficiency driving changes in a viral genome, permitting an avirulent virus to acquire virulence due to genetic mutation.Abstract:
Previous work from our laboratory demonstrated that selenium deficiency in the mouse allows a normally benign (amyocarditic) cloned and sequenced Coxackievirus to cause significant heart damage. Furthermore, Coxsackievirus recovered from the hearts of selenium-deficient mice inoculated into selenium-adequate mice still induced significant heart damage, suggesting that the amyocarditic Coxsackievirus had mutated to a virulent phenotype. Here we report that sequence analysis revealed six nucleotide changes between the virulent virus recovered from the selenium-deficient host and the avirulent input virus. These nucleotide changes are consistent with known differences in base composition between virulent and avirulent strains of Coxsackievirus. To the best of our knowledge, this is the first report of a specific nutritional deficiency driving changes in a viral genome, permitting an avirulent virus to acquire virulence due to genetic mutation.read more
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References
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Journal ArticleDOI
Oxidants, antioxidants, and the degenerative diseases of aging
TL;DR: It is argued that this damage to DNA, protein, and lipid is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts.
Journal ArticleDOI
Rapid evolution of RNA genomes
John J. Holland,Katherine R. Spindler,Katherine R. Spindler,Frank M. Horodyski,Elizabeth A. Grabau,Stuart T. Nichol,Scott VandePol +6 more
TL;DR: RNA viruses show high mutation frequencies partly because of a lack of the proofreading enzymes that assure fidelity of DNA replication, and high rates of replication reflected in rates of RNA genome evolution which can be more than a millionfold greater than the rates of the DNA chromosome evolution of their hosts.
Journal ArticleDOI
Spontaneous point mutations that occur more often when advantageous than when neutral.
TL;DR: It is shown that point mutations in the trp operon reverted to trp+ more frequently under conditions of prolonged tryptophan deprivation when the reversions were advantageous, than in the presence of tryPTophan when the reversal were neutral, and a heuristic model for the molecular basis of such mutations is proposed.
Journal ArticleDOI
Complete nucleotide sequence of infectious Coxsackievirus B3 cDNA: two initial 5' uridine residues are regained during plus-strand RNA synthesis.
TL;DR: It is reported that cDNA-generated CVB3, as well asCVB3 generated by in vitro-synthesized RNA transcripts, regains the authentic initial 5' uridine residues during replication in transfected cells, indicating that the picornaviral primer molecule VPg-pUpU may be uridylylated in a template-independent fashion.