While early responses to MCMV infection in the liver are well understood, it remains unclear how the virus is sensed in this compartment. This is in contrast with other sites, namely the spleen, in which studies by our group and others have definitively shown a role for TLR9 and MyD88 signaling in IFN-a, proinflammatory cytokine and cellular responses in addition to restriction of virus replication [6, 20, 31, 32] . Although TLR7 alone does not appear to have a strong role in MCMV recognition, TLR7 and TLR9 combined deficiency was shown to severely impair pDC responses against MCMV in the spleen [33] . A significant but minor role for TLR3 signaling in the spleen has also been suggested in response to MCMV infection [6] . In the liver, however, studies by our group have demonstrated that early innate responses are TLR9-independent but MyD88-dependent [20] . Liver pDCs from mice genetically deficient in TLR9 produce wild-type (WT) levels of IFN-a at 40 h post-MCMV infection, with intact downstream cellular and proinflammatory cytokine responses. Further, TLR9-deficient mice do not exhibit elevated liver viral titers. Conversely, MyD88-deficient mice have severely impaired liver cytokine and cellular responses, and are unable to control virus replication in this compartment [20, 32] . MyD88 is a common adaptor molecule for TLR9 and TLR7 signaling; however, evaluation of TLR7-deficient mice also demonstrated that TLR7 signals alone were not required to initiate liver antiviral defense [20] .