Coxsackievirus B3 induction of NFAT: requirement for myocarditis susceptibility.
Ultraviolet (u.v.) inactivated coxsackievirus B3 (CVB3) induces rapid calcium flux in naïve BALB/c CD4+ T cells. 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. FasL expression by V gamma 4+ cells was also suppressed. Inhibition of FasL expression by V gamma 4+ cells is consistent with myocarditis protection in dnNFAT mice.
Huber
S A
SA
Department of Pathology, University of Vermont, Colchester, VT 05446, USA. Sally.Huber@uvm.edu
Rincon
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003384:Coxsackievirus Infections / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D004198:Disease Susceptibility / Q000378:metabolism; D029822:Enterovirus B, Human / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009205:Myocarditis / Q000276:immunology / Q000503:physiopathology* / Q000821:virology*; D009206:Myocardium / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010179:Pancreas / Q000473:pathology; D013154:Spleen / Q000166:cytology
D050778:NFATC Transcription Factors; D002118:Calcium