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Genomic regions of coxsackievirus B3 associated with cardiovirulence
1Department of Microbiology, University of Arkansas for Medical Science, Little Rock, USA.
Insights
The 5' nontranslated region (NTR) of coxsackievirus B3 (CVB3) is the primary determinant of cardiovirulence. Specific capsid proteins also contribute to CVB3
Area of Science:
- Virology
- Molecular Biology
- Cardiology
Background:
- Coxsackievirus B3 (CVB3) is a significant cause of viral myocarditis.
- Understanding the genetic basis of CVB3 cardiovirulence is crucial for developing therapeutic strategies.
Purpose of the Study:
- To elucidate the molecular determinants of cardiovirulence within the CVB3 genome.
- To identify specific viral genomic regions responsible for CVB3-induced myocarditis.
Main Methods:
- Construction and analysis of infectious chimeric cDNAs from virulent (CVB3m) and non-virulent (CVB30) CVB3 strains.
- Assessment of cardiovirulence in a murine model of acute myocarditis.
- Comparative analysis of nucleotide and amino acid sequences in key viral genomic regions.
Main Results:
- The 5' nontranslated region (5' NTR) of the CVB3 genome plays a major role in determining cardiovirulence.
- The genomic region encoding capsid proteins contributes a minor, additive effect to cardiovirulence.
- Sequence variations within the 5' NTR, particularly in stem-loop motifs, and specific amino acid changes in VP2 and VP3 are implicated in cardiovirulence.
Conclusions:
- Cardiovirulence in CVB3 is a multifactorial trait influenced by both the 5' NTR and capsid protein-encoding regions.
- Specific sequence elements within the 5' NTR and capsid proteins are critical for CVB3's ability to cause myocarditis.
Abstract:
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.