Coxsackievirus B3 clinical isolates and murine myocarditis

Fifteen clinical coxsackievirus B3 (CVB3) isolates were assessed for cardiopathologic capabilities in adolescent male CD-1 mice in comparison to two well characterized cardiovirulent CVB3 strains. One isolate was cardiovirulent, one minimally cardiovirulent and the remaining 13 isolates were noncardiovirulent. The two cardiovirulent isolates and one well characterized cardiovirulent strain, established higher viremic titers, in comparison to five noncardiovirulent isolates that were examined. The two cardiovirulent isolates and one well characterized cardiovirulent strain replicated to significantly higher titers than five noncardiovirulent isolates in primary cultures of murine neonatal or adolescent cardiac fibroblasts. Nucleotide sequence analysis of an area defined by nucleotides (N)300-N599 in the 5′-nontranslated region were performed on the two well characterized cardiovirulent CVB3 strains, the two cardiovirulent isolates and 12 noncardiovirulent isolates. The data detected a single discriminatory nucleotide position. An A was present at N565 in three of four cardiovirulent CVB3, whereas a U or C was present in this position in 12 of 12 noncardiovirulent CVB3. In toto, these data are compatible with the hypothesis that the type of the nucleotide at N565, a position within the internal ribosome entry site, is associated with capacity of a CVB3 for replication in vivo and in vitro and this capacity for vigorous replication is associated with cardiovirulence.