although it can also infect T cells, NK cells, and epithelial cells. Both the attachment of EBV to receptor CD21 and the interaction of the virus glycoprotein gp350-gp250 with TLR2 activate NF-κB [62] . The virus gB and gH proteins are also candidates for TLR2 ligands. Immortalization of B cells by EBV infection is due to the activation of NF-κB by the latent membrane protein 1 (LMP1), and antigen stimulation-like signaling of the B cell receptor by LMP-2. TLR2 signaling suppresses the transcription of the TLR9 gene via activation of NF-κB containing p65 protein. So downregulation of TLR9 and upregulation of TLR7 and MyD88 are observed in EBV-infected cells [63] . Cell proliferation is thought to be driven by TLR7 signaling activated by virus RNA, because the TLR7 antagonist IRS661 suppresses cell division. Small RNA encoded by the EBV genome (EBV-EBERs) activates TLR7 signaling, and induces IL-10 production. TLR7 signaling also upregulates and activates IRF-5, and induces proinflammatory cytokines. However, activated IRF-5 is negatively regulated by EBV-induced IRF-4 and a splice variant of IRF-5 (V12IRF-5) [63] . This suggests that the TLR7 signaling system play a role in the cell division of EBVinfected cells, and in the establishment of persistent infection. Lytic infection and production of virus particles are observed during the late stage of EBV infection. Late proteins suppress NF-κB activation. This leads to the downregulation of proinflammatory cytokines, the upregulation of TLR9, and the suppression of TLR7 function through interaction of TLR7 and TLR9. So the TLR9 system should be important during late stage of EBV infection.