Coxsackievirus B3 replication is related to activation of the late extracellular signal-regulated kinase (ERK) signal

MAP kinase signaling has been implicated in coxsackievirus B3 (CVB3) pathogenesis and as necessary in the virus lifecycle. We studied the correlation with extracellular signal-regulated kinase 1/2 (ERK1/2) signaling and virus replication in the presence of coxsackievirus and adenovirus receptor (CAR). In CHO cells that do not expressed CAR, specific ERK1/2 phosphorylation (pERK1/2) was not detected, and progeny virus was not produced after infection. By contrast, in HeLa and CHO-CAR cells, which expressed CAR, the specific early and late pERK1/2 at 0.5 and 8 h were induced, and progeny viruses were produced progressively through 24 h after infection. However, when CHO-CAR cells were infected with replication-defective CVB3, specific pERK1/2 was not detected. In addition, when late pERK1/2 is inhibited by the MEK1 inhibitor PD98059, at 4 h after infection, virus replication significantly decreased. Therefore, our findings suggest that early pERK1/2 is a response to virus binding to CAR, whereas late pERK1/2 is related to the viral replication.