The activity of ERK is associated with the expression of type I IFN and cytokines, particularly IL-10 [31, 32, 33] . We thus further checked whether DENV-2 targets ERK activation by examining the phosphorylated ERK (p-ERK). DENV-2 infection did not activate ERK1/2 phosphorylation and even impaired the basal level of p-ERK1/2 ( Figure 5A ). Furthermore, polyI:C-and LPS-stimulated phosphorylation of ERK1/2 was decreased with DENV-2 infection ( Figure 5B and 5C), so DENV blocks TLR-mediated ERK activation to modulate both arms of the innate immunity response to infection: type I IFN and cytokines.