Fig. 8

Proposed model of MEK as a key regulatory pathway of the IFN response against RV and RSV in airway epithelial cells. PI3K activation leads to activation of the AKT pathway following MEK inhibition. Upon RV or RSV infection, TLR3/RIG-I sensors activate the IRF3 pathway, which enables the transcription of type I and III IFN genes. At early stage of the infection, AKT induces deactivation of the translational repressor 4E-BP1 by phosphorylation and activation of p70S6K by phosphorylation, which eventually promote initiation of mRNA translation of IFN related genes. At late stage of a potent viral infection (RSV), MEK inhibition decreases STAT3 activation, which results in the reduction of the expression of the transcription repressor of IFNB1 gene, PRDI-BF1, thereby creating a supplementary positive feedback loop