FIG 3.

Cell entry and innate immune response. HPeV attaches to the cell surface by interaction of the RGD motif with αVβ1 integrin. The clathrin-dependent pathway facilitates the internalization of HPeV into endosomes, where a signaling cascade is mediated. Upon the activation of TLR7 and TLR8, the adaptor protein MyD88 stimulates NF-κB expression. The cooperative binding of the NF-κB p65 subunit, IFN regulatory factor 3 (IRF-3), and activator protein 1 (AP-1) to the type I IFN promoter region of the DNA induces IFN-β gene transcription (20), which results in the induction of the proinflammatory cytokines IFN-β, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) (49).