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. Infectious cDNAs representing a highly cardiovirulent coxsackievirus B3 (CVB3m) and a noncardiovirulent (CVB30) virus were used to construct infectious chimeric cDNAs. Assays of the resulting recombinant viruses for cardiovirulence in adolescent male CD-1 mice showed that the 5' nontranslated region (5' NTR) of the CVB3m genome plays the major role in determining cardiovirulence and that the genomic region encoding the capsid proteins has a minor additive effect in increasing cardiovirulence. Nucleotide sequences in the 5' NTR of CVB3m and CVB30 differ at 23 positions; 14 are located in four stemloop motifs of the secondary structure and may influence the cardiovirulent phenotype by regulating RNA or protein synthesis. A comparison of predicted amino acid sequences of capsid proteins in CVB3m and CVB30 identified two amino 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 external surface. The data from this study and published literature support the conclusion that cardiovirulence of a CVB3 can depend on several regions of the genome.
Lee
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C
Department of Microbiology, University of Arkansas for Medical Science, Little Rock, USA.
Maull
E
E
Chapman
N
N
Tracy
S
S
Gauntt
C
C
D000818:Animals; D001665:Binding Sites; D003384:Coxsackievirus Infections / Q000821:virology*; D029822:Enterovirus B, Human / Q000235:genetics* / Q000472:pathogenicity*; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000821:virology*; D014774:Virulence / Q000235:genetics