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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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TLDR
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.

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Citations
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Journal ArticleDOI

Glutathione is required for efficient production of infectious picornavirus virions.

TL;DR: It is demonstrated that glutathione is important for production of mature infectious picornavirus virions, whereas cells treated with BSO exhibit increased replication of Sendai virus.
Journal ArticleDOI

Generation of an infectious cDNA of a highly cardiovirulent coxsackievirus B3(CVB3m) and comparison to other infectious CVB3 cDNAs

TL;DR: P phenotypic diversity of CVB3 within the prototype Nancy strain is an example of RNA viruses adapting to changing environments (cells, mice and humans) through mutations and selective pressure.
Journal ArticleDOI

Selenium levels in relation to morbidity and mortality among children born to HIV-infected mothers

TL;DR: Among infants born to HIV-infected women in sub-Saharan Africa, selenium status may be important to prevent child mortality, and preliminary findings warrant future reexamination.
Book ChapterDOI

Pathophysiological Effects of High-Output Production of Nitric Oxide

TL;DR: The discovery of an accelerated viral mutation rate in the host during viral infection is discussed from the perspective of NO-induced oxidative stress, and Mechanisms of carcinogenesis involving free radicals formed in the course of chronic infectious diseases are described.

Dietary selenium: Time to act - Low bioavailability in Britain and Europe could be contributing to cancers, cardiovascular disease, and subfertility

TL;DR: Selenium is a key component of a number of functional selenoproteins required for normal health and can decompose to give further reactive free radicals and cytotoxic aldehydes, which initiate more lipid peroxidation, promote atherosclerosis, damage DNA, and metabolically activate carcinogens.
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

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 Article

Viral myocarditis. A review.

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.
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