Enhanced ERK-1/2 activation in mice susceptible to coxsackievirus-induced myocarditis
J. Clin. Invest. Mary Anne Opavsky, et al. 109:1561 doi:10.1172/JCI13971 [
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Figure 3CVB3 replication in Jurkat cells is regulated by Src’s and the ERK-1/2 signaling pathway. To assess infectivity, T cell lines (10
6) were treated with kinase inhibitors in DMSO or with DMSO alone (0) for 1 hour at 37°C, and then cells were infected with CVB3 (moi = 1) as described in Methods. Following incubation at 37°C for 48 hours, cells were frozen, then viral titers were determined by plaque assay. Treatment of (
a) Jurkat and (
b) JCaM cells with the MEK-1/2 inhibitor UO126 decreased CVB3 titers in Jurkat cells, but did not affect viral production in JCaM cells at the same doses of inhibitor. Treatment of (
c) Jurkat and (
d) JCaM cells with the MEK-1/2 inhibitor PD98059 significantly decreased CVB3 titers in Jurkat cells, but not in JCaM cells. Treatment of (
e) Jurkat and (
f) JCaM cells with the Src inhibitor PP2 decreased CVB3 titers in Jurkat cells, but not in JCaM cells. Titers were increased in JCaM cells treated with 0.5 μM PP2. Virus titers are expressed as mean pfu/10
6 cells (± SEM,
n = 3 per group). *
P < 0.05 DMSO versus kinase inhibitor for each cell type (ANOVA plus Bonferroni/Dunn post hoc testing).