. HCV does not only infect hepatocytes. It can also infect DCs, macrophages, monocytes, and T lymphocytes. However, the virus does not replicate efficiently in these cell types. Although, virus particles and virus proteins are found in the blood of HCV patients. HCV causes no cytopathic effects. Immune responses against HCV may be weak, but infected cells are attacked and eliminated. In order to survive in the host, HCV maintains a chronic infection by suppressing the host immune responses. Both HCV core and NS3 proteins activate NF-κB and AP-1 via stimulation of TLR2, which requires TLR1 and TLR6 as costimulators, in monocytes and Kupffer cells [28] . This activation leads to the production of IL-10 and TNF-α, both found in HCV patients at a high titer. IL-10 suppresses the maturation of pDCs and the activation of T lymphocytes, and induces apoptosis in pDCs. The NS3-NS4A protein complex, which is a serine protease, degrades TRIF and IPS-1/Cardif/MAVS/VISA, which are essential for cellular signaling via TLR3, TLR4, and RIG-I [29] . This shutting off of TRIF-and IPS-1-dependent signaling results in the suppression of IFN-α and IFN-β production, and in dysfunction of mDCs. The NS5A protein suppresses activation of IRAK-1 through its interaction with MyD88. This leads to the shutting off of TLR7 and TLR8 signaling, and to the suppression of maturation and differentiation of pDCs [30] . On the other hand, NF5A suppresses TRAF2 dependent NF-κB activation via interaction with NF5A and TRAF2, but suppress neither MEK1 activation nor IKKβ-dependent NF-κB activation [31] . TNF-α-dependent activation of JNK is enhanced. Infected DCs are thought to affect the production of TNF-α, TNF-α signal transduction, and chemotaxsis and maturation. Dysfunction of DCs, suppression of T lymphocyte activation, and a decrease in DC number due to apoptosis allow HCV to establish a chronic infection [32] . It has also been reported that HCV-specific cytotoxic T lymphocytes share upregulated expression of the coinhibitory molecule PD-1, and that signaling from PD-1L (PD-1 ligand) on DCs results in suppression of HCV-specific cytotoxic T lymphocytes [33] .