What question did this study set out to answer?

To identify the natural genetic sequences responsible for cardiovirulence in clinical isolates of Coxsackievirus B3 (CVB3).

May 15, 2000Journal of VirologyOpen Access

Genomic Determinants of Cardiovirulence in Coxsackievirus B3 Clinical Isolates: Localization to the 5′ Nontranslated Region

Q: What is the clinical evidence from this study?

Study design: Other. Population: Coxsackievirus B3-induced myocarditis. Intervention: Chimeric CVB3 viruses (5'NTR and capsid exchanges) vs. Parental CVB3 strains. Primary outcome: Myocarditis lesion score and cardiac viral titer.

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Key result

Replacement of the CVB3 5'NTR with sequences from a noncardiovirulent strain ablated myocarditis in mice, identifying the 5'NTR as the primary determinant of the natural cardiovirulence phenotype.

Population

C3H/HeJ mice (murine model of inflammatory heart disease)

Comparison

Inoculation with intratypic chimeric… vs Chimeric strains with different sequence…

Design

Preclinical

Follow-up

10 days

Authors

JDJames J. DunnTexas Children's Hospital NCNora M. ChapmanCreighton University STSteven TracyUniversity of Nebraska Medical Center

Discussion

Member takes

Implication

No immediate clinical implications for enteroviral myocarditis; leaves open 5'NTR as a target for attenuation studies.

Key Points

To identify the natural genetic sequences responsible for cardiovirulence in clinical isolates of Coxsackievirus B3 (CVB3).
Constructed six intratypic chimeric viruses by replacing the 5' nontranslated region (5'NTR) and capsid sequences of cardiovirulent CVB3/20 cDNA with homologous sequences from noncardiovirulent (CVB3/CO) or cardiovirulent (CVB3/AS) clinical strains.
Inoculated C3H/HeJ mice with chimeric strains and evaluated myocarditis and myocardial viral presence at 10 days postinoculation using light microscopy and viral recovery assays.
Recombinant viruses carrying the noncardiovirulent CVB3/CO 5'NTR (either alone or paired with capsid sequences) failed to induce myocarditis and yielded no recoverable infectious virus from the myocardium.
Chimeras with CVB3/CO capsid substitutions alone retained the cardiovirulent phenotype and supported viral recovery at 10 days, while chimeras with CVB3/AS 5'NTR or capsid segments consistently preserved myocarditic activity.

Structured PICO

Population

Juvenile male C3H/HeJ mice inoculated with chimeric Coxsackievirus B3 strains to evaluate myocarditis at 10 days postinoculation.

Intervention

Inoculation with intratypic chimeric Coxsackievirus B3 (CVB3) strains containing 5'NTR and/or capsid sequences from clinical isolates (CVB3/CO or CVB3/AS)

Comparator

Chimeric strains with different sequence replacements

Outcome

Evidence of myocarditis by light microscopy and presence of virus in the myocardium at 10 days postinoculationsurrogate

The 5' nontranslated region (5'NTR) is the primary genomic determinant of the natural cardiovirulence phenotype in Coxsackievirus B3 clinical isolates.

Limitations

Other viral genomic regions (e.g., capsid) may contain additional determinants that modulate the expression of the 5'NTR phenotype.
The specific sites within the 5'NTR and molecular mechanisms determining the phenotype remain to be identified.

Cite This Study

Dunn et al. (2000) studied Coxsackievirus B3-induced myocarditis. Chimeric CVB3 viruses (5'NTR and capsid exchanges) vs. Parental CVB3 strains was evaluated on Myocarditis lesion score and cardiac viral titer. Replacement of the CVB3 5'NTR with sequences from a noncardiovirulent strain ablated myocarditis in mice, identifying the 5'NTR as the primary determinant of the natural cardiovirulence phenotype.

synapsesocial.com/papers/6a8ed1d23d91093f4f11e58f https://doi.org/10.1128/jvi.74.10.4787-4794.2000

Topics

Myocarditis

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