GENOMIC REGIONS OF COXSACKIEVIRUS B3 ASSOCIATED WITH CARDIOVIRULENCE

The molecular basis for cardiovirulence in the coxsackievirus B3 (CVB3 ) genome was examined in a murine model of acute myocarditis. Infectio us cDNAs representing a highly cardiovirulent coxsackievirus B3 (CVB3( m)) and a noncardiovirulent (CVB3(o)) virus were used to construct inf ectious chimeric cDNAs. Assays of the resulting recombinant viruses fo r cardiovirulence in adolescent male CD-1 mice showed that the 5' nont ranslated region (5' NTR) of the CVB3(m) genome plays the major role i n determining cardiovirulence and that the genomic region encoding the capsid proteins has a minor additive effect in increasing cardiovirul ence. Nucleotide sequences in the 5' NTR of CVB3(m) and CVB3(o) differ at 23 positions; 14 are located in four stem-loop motifs of the secon dary structure and may influence the cardiovirulent phenotype by regul ating RNA or protein synthesis. A comparison of predicted amino acid s equences of capsid proteins in CVB3(m) and CVB3(o) identified two amin o acids as potential candidate contributors to cardiovirulence, i.e., amino acids at positions A207 (Asn-Asp) in the puff structure of the E -F loop of VP2 and A566 (Gln-Glu) in the C terminal of VP3 at the exte rnal surface. The data from this study and published literature suppor t the conclusion that cardiovirulence of a CVB3 can depend on several regions of the genome. (C) 1997 Wiley-Liss, Inc.