Murine coxsackie virus B3 myocarditis

Adolescent male CD-1 mice inoculated with a coxsackie virus B3 variant (CVB3(m)) develop an acute myocarditis. The heart contains large numbers of fibroblasts, and infected fibroblasts can serve as target cells for sensitized cytotoxic T lymphocytes. These facts led us to study the interaction of CVB3(m) with fibroblast cultured from murine infant or adolescent heart tissues, or neonatal skin. Approximately 12-24% of cells in all fibroblast cultures are immunofluorescence-positive, and some cultures produce virus for up to 12 days in the absence of cytopathology. Infected, but not uninfected, skin fibroblasts exhibit an altered surface, detectable by binding of the lectin Ulex europaeus agglutinin I (UEAI). Beta interferon treatment of skin fibroblasts prior to infection with CVB3(m) or infection with an amyocarditic variant of CBV3 results in reduced UEAI binding. Interaction of virus-activated natural killer cells with CBV3(m)-infected skin fibroblasts results in significantly reduced virus yields. Cloned lines of SV₄₀-transformed skin fibroblasts were established. The majority (71%) exhibit no cytopathology, and over half replicate CVB3(m) to high titres, although in some permissive lines only up to 16% of cells are immunofluorescence-positive. These data suggest that virus infection of a subset(s) of cardiac fibroblasts results in replication and induction of a surface neoantigen(s) which activates NK cells for some protection, but the neoantigen(s) induces deleterious cell-mediated/delayed hypersensitivity mechanisms.