RAPID GENOMIC EVOLUTION OF A NONVIRULENT COXSACKIEVIRUS B3 IN SELENIUM-DEFICIENT MICE RESULTS IN SELECTION OF IDENTICAL VIRULENT ISOLATES

Previous work from our laboratory demonstrated that selenium deficienc y in the mouse allows a normally benign (amyocarditic) cloned and sequ enced Coxsackievirus to cause significant heart damage. Furthermore, C oxsackievirus recovered from the hearts of selenium-deficient mice ino culated into selenium-adequate mice still induced significant heart da mage, suggesting that the amyocarditic Coxsackievirus had mutated to a virulent phenotype. Here we report that sequence analysis revealed si x nucleotide changes between the virulent virus recovered from the sel enium-deficient host and the avirulent input virus. These nucleotide c hanges are consistent with known differences in base composition betwe en virulent and avirulent strains of Coxsackievirus. To the best of ou r knowledge, this is the first report of a specific nutritional defici ency driving changes in a viral genome, permitting an avirulent virus to acquire virulence due to genetic mutation.