A significant reduction in the number of virus-induced myocardial lesions was effected by administration of murine interferon beta (IFN-beta) or polyriboinosinic: polyribocytidylic acid copolymer (pI:pC) at -24, 0, or 24 h but not 72 h postinoculation (p.i.) of coxsackie-virus B3 (CVB3) to adolescent CD-1 mice. Inoculation of interferon at any of the four times did not reduce virus titers in heart tissues at three or seven days p.i., but inoculation of pI:pC at -24, 0, or 24 h p.i. significantly reduced virus titers. Administration of anti-murine IFN-beta at 72 h p.i. significantly reduced myocarditic lesion numbers. The results suggest that there are two identifiable times after CVB3 inoculation in which interferon may play a role in CVB3-induced myocarditis: a very early time (+/- 24 h of virus entry) in which the presence of interferon is beneficial to the animal and a later time (72 h p.i. of virus) in which absence of interferon is beneficial to the animal. In vitro studies on the effects of IFN-beta or anti-IFN-beta antiserum on replication of CVB3 in permissive primary cultures of murine neonatal skin fibroblasts show that this virus is sensitive to the antiviral action of interferon which is produced in infected cultures.

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Replication of coxsackievirus B3 occurred for days in cultures of murine neonatal skin fibroblasts in the absence of cytopathology and resulted in alteration of the plasma membrane. Dual immunofluorescence studies showed that the lectin Ulex europaeus agglutinin I bound only to cells producing viral capsid antigens. Cultures of coxsackievirus B3-inoculated murine neonatal skin fibroblasts showed maximum binding of this lectin at 72 h postinoculation. These data show that in a nonlytic infection a picornavirus can alter the surface of an infected cell.

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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.