Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets
Key result
Coxsackievirus B3 infection in mice targets immune cells, particularly B cells, providing a noncardiac reservoir for viral RNA during acute and persistent myocardial enterovirus infection.
Population
Immunocompetent mice (SWR/J, H-2q)
Design
Preclinical
Authors
Discussion
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Implication
Identifies B-cell reservoirs in murine coxsackievirus myocarditis; hypothesis-generating for human persistence, no clinical implications yet.
Key Points
- To identify specific organ and cellular targets supporting persistent coxsackievirus B3 (CVB3) infection and dissemination in an immunocompetent mouse model of myocarditis.
- Inoculated immunocompetent SWR/J (H-2q) mice intraperitoneally with coxsackievirus B3 (CVB3).
- Mapped tissue dissemination and viral persistence across multiple organs using in situ hybridization to detect enteroviral genomic RNA and replicative minus-strand RNA intermediates.
- Identified infected lymphoid cell subsets by simultaneously staining spleen sections for enteroviral RNA and cell-specific surface markers (CD45R/B220, CD4, CD8, and Mac-1).
- During acute infection, viral RNA was detected at high levels in the myocardium, pancreas, spleen, and lymph nodes, with lower levels found in the central nervous system, thymus, lung, and liver.
- At late stages of disease, enteroviral RNA restricted its persistence exclusively to the myocardium, spleen, and lymph nodes.
- Infected spleen cells in acute disease primarily comprised CD45R/B220+ B cells, along with CD4+ helper T cells and Mac-1+ macrophages (excluding CD8+ T cells), while persistent infection localized to replicating B cells in secondary follicle germinal centers.
Structured PICO
P
Population
Immunocompetent mice (SWR/J, H-2q)
I
Intervention
Intraperitoneal inoculation with coxsackievirus B3 (CVB3)
O
Outcome
Localization of enteroviral RNA and cell-specific surface antigens in organs and immune cellssurrogate
Immune cells, specifically B cells, act as a noncardiac reservoir for viral RNA during acute and persistent coxsackievirus B3 myocarditis.
Cite This Study
Klingel et al. (1996) studied Enterovirus myocarditis. Coxsackievirus B3 (CVB3) inoculation was evaluated on Organ and cellular targets of persistent enterovirus infection. Coxsackievirus B3 infection in mice targets immune cells, particularly B cells, providing a noncardiac reservoir for viral RNA during acute and persistent myocardial enterovirus infection.