Fig. 2

Mechanism of responses of TLRs to EBV and HCMV. EBV activates the MyD88 pathway or the MyD88-independent pathway via the viral envelope and products. Upon EBV stimulation, TLR2, TLR3, TLR7, and TLR9 inside and outside the cells induce NF-κB or IRF-5/7 by a series of protein kinases to produce cyto-inflammatory factors. MyD88 recruits TRAF6 and IRAKs to activate the IKK complex composed of IKKα, IKKβ, and NEMO. Besides acting as an inflammatory mediator, NF-κB also upregulates the expression of LMP1 to trigger moderate inflammation. Similarly, HCMV reacts with TLRs, including TLR2, TLR3, TLR4, and TLR9, through the viral envelope or products. MyD88-NF-κB is the main pathway. However, dsRNA from CMV also activates IRF-3 and TLR3 to promote the expression of inflammatory factors. Meanwhile, the CMV-encoded miR-UL112-3p inhibits activation of the TLR2/NF-κB pathway, as well as the expression of various cytokines