Coxsackievirus B3 induction of NFAT: Requirement for myocarditis susceptibility

Ultraviolet (u.v.) inactivated coxsackievirus B3 (CVB3) induces rapid calcium flux in naive BALB/c CD4+ Tcells. CD4+ cells lacking decay accelerating factor (DAF-/-) show little calcium flux indicating that virus cross-linking of this virus receptor protein is necessary for calcium signaling in CVB3 infection. Interaction of CVB3 with CD4+ cells also activates NFAT DNA binding. To show that NFAT activation is crucial to CVB3 induced disease, wild-type mice and transgenic mice expressing dominant-negative NFAT (dnNFAT) Mutant in T cells were infected and evaluated for myocarditis and pancreatitis 7 days later. Inhibition of NFAT in T cells prevented myocarditis but had no effect on pancreatitis. Virus titers in pancreas were equivalent in wild-type and dnNFAT animals but cardiac virus titers were increased in dnNFAT mice. Interferon-gamma (IFN gamma) expression was reduced in both CD4+ and V gamma 4+ T cells from dnNFAT mice compared to controls. Fast, expression by V gamma 4+ cells was also Suppressed. Inhibition of Fast expression by V gamma 4+ cells is consistent with myocarditis protection in dnNFAT mice. (C) 2008 Elsevier Inc. All rights reserved.