Fig. 1

TLR-mediated signaling pathways in response to HSV. Upon HSV ligand stimulation, TLR2, TLR4, and TLR9 recruit the adaptor MyD88. Once recruited, MyD88 binds the protein complex composed of IRAK and TRAF6. TRAF6 results in the phosphorylation of TAK1, which then activates the IKK complex that results in the phosphorylation and degradation of IκB. The degradation of IκB allows NF-κB to translocate into the nucleus. Alternatively, TAK1 activates the MAPK pathway, triggering the activation of AP-1. Under HSV stimulation, TLR3 is localized and phosphorylated by tyrosine kinase c-Src, EGFR, and PI3K in the endosome. Moreover, TLR3 triggers TRIF to enable TBK1, IKKε, NAP1, and TRAF3 to generate a complex. Furthermore, this complex leads to the activation of IRF3/IRF7 and NF-κB. TLR3 recruits TRAF and RIP1 to phosphorylate TAB2 and TAK1. The complex formed by TAB2 and TAK1 activates AP-1 via the MAPK pathway and NF-κB via the IKK complex-IκB pathway. Together, NF-κB, IRF3/IRF7 and AP-1 induce the expression of inflammatory cytokines to protect the host by innate immunity