Cellular immune responses in mice challenged with an amyocarditic variant of coxsackievirus B3

Abstract

An amyocarditic variant of a temperature-sensitive (ts) mutant derived from the parent myocarditic variant Coxsackievirus B3 (CVB3m) was studied in a murine model of CVB3m-induced myocarditis to assess virus-induced antigens and their possible role in the disease process. Amyocarditic variant ts5R induced a heart tissue antigen(s), extractable by hypertonic KC1, which inhibited migration of peritoneal exudate cells from CVB3-inoculated myocarditic mice in an agarose droplet cell-migration-inhibition assay. The ts5R variant was amyocarditic at inoculum doses of 10(3) to 10(8) plaque-forming units per mouse, but in cyclophosphamide-immunosuppressed mice, ts5R induced myocarditis. Viable ts5R served as a vaccine and protected mice against CVB3m-induced myocarditis. Murine neonatal skin fibroblasts (MNSF) infected with either virus served as in vitro targets and were lysed by splenic cytotoxic T lymphocytes from mice inoculated with either virus variant. ts5R and CVB3m replicated to similar titers in murine neonatal skin fibroblasts (MNSF) at 24 hr postinoculation (pi), but differences in titers were found by 72 hr pi. Levels of natural killer cell activities in spleens of ts5R-inoculated mice were slightly lower than in spleens of CVB3m-inoculated mice at 7 days pi. The data suggest that viral induction of new antigens on target cells and viral induction of specific cytotoxic T lymphocytes that recognize these antigenic changes do not always result in induction of myocarditis.

Coxsackievirus B3 infection alters plasma membrane of neonatal skin fibroblasts

“…Previous studies from our laboratories with mouse (5,6,11,(15)(16)(17) and baboon (14) models of CVB3,,-induced myocarditis showed that heart tissues from CVB3,,inoculated animals with myocarditis (but not from normal animals) contained a new nonvirion KCl-extractable antigen(s). This antigen(s) evoked a specific immune response.…”

Role of natural killer cells in experimental murine myocarditis

“…In this animal model, doses of 102 or 103 pfu are submyocarditic, thus NK cell activation does not depend on induction of myocarditis. Indeed, an amyocarditic variant of CVB3 induces comparable NK cell activation in CD-1 mice [16,26].…”