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Coxsackievirus B4 heterogeneity: effect of passage on neutralization and mortality
Insights
Two Coxsackievirus B4 (CB4) isolates showed stable virulence and tissue tropism in mice. Despite significant antigenic variation, laboratory strains may retain virulence similar to fresh isolates.
Area of Science:
- Virology
- Immunology
- Pathogen Research
Background:
- Coxsackievirus B4 (CB4) is a significant human pathogen.
- Understanding CB4 isolate virulence and antigenic properties is crucial for disease control.
Purpose of the Study:
- To compare two CB4 isolates regarding virulence, tissue tropism, and antigenic drift.
- To assess the stability of virulence and phenotypic characteristics upon passage.
- To evaluate the influence of isolation source on virulence.
Main Methods:
- Comparison of two CB4 isolates (Edwards and JVB) in C57B1/6 and Balb/c mice.
- Assessment of viral replication, tissue tropism, and lethal infection.
- Use of monoclonal antibodies to detect antigenic variation.
- In vitro and in vivo passage experiments to evaluate virulence stability.
Main Results:
- Both CB4 isolates replicated in mice, with the Edwards isolate causing lethal infections.
- Lethal infections correlated with high viral titers in visceral organs.
- Virulence and avirulence phenotypes remained stable upon passage.
- Significant antigenic variation was observed among isolates.
- Isolation site and cell line did not significantly impact virulence.
Conclusions:
- CB4 virulence is stable during extended in vitro and limited in vivo passage.
- Isolation site and method do not appear to select for or against virulence.
- Laboratory-adapted CB4 strains may retain virulence similar to fresh isolates despite antigenic differences.
Abstract:
We have compared two CB4 isolates for virulence, tissue tropism, and antigenic drift using monoclonal antibodies. Both isolates replicated in C57B1/6 and Balb/c mice. The human isolate Edwards, recovered from a fatal case of encephalohepatomyocarditis, produced lethal infection in adult animals. Lethal infections were associated with high viral titers in visceral organs but not with the presence of specific neutralizing epitopes. Virulence seemed stable upon passage, and also the avirulent JVB isolate retained its phenotype. Mock infection and recovery experiments demonstrated the stability of these characteristics. Neither the tissue from which the virus was isolated nor the cell line used in isolation significantly reduced virulence. However, antigenic variation among isolates was abundant. Thus, the set of monoclonal antibodies employed here may not be appropriate positive markers for virulence. This study suggests that CB4 virulence is stable upon extended in vitro passage and limited in vivo passage and that isolation site and method may not select for or against virulence. It is therefore possible that laboratory adapted strains of CB4, although antigenically different from freshly isolated specimens, may still retain these properties responsible for virulence present in low passage isolates and may be, with regard to virulence, very similar to freshly isolated specimens.