In conclusion, this study indicates that UNC93B1, which is essential for combined endosomal TLR signaling, contributes to development of effective innate immune responses to an acute Figure 6 . Effect of the 3d mutation on viral clearance. Livers were harvested from C57BL/6 (WT) or 3d mice that were either uninfected or infected for 3, 5, 7 or 9 days with MCMV (5610 4 PFU). Viral titers were determined using a standard plaque assay. The level of detection of the plaque assay is 2 log PFU/g liver (dashed line). Each data point represents an individual WT (filled diamonds) or 3d mouse (open circles). Data from days 0, 3, 5, and 7 are the combined results of three independent experiments (n = 4-7 mice per group). In data from day 9, n = 5 mice per group. Asterisks denote a significant difference between WT and 3d mean PFU/g liver (p values#0.04). doi:10.1371/journal.pone.0039161.g006 virus infection in the liver. Our results show that this contribution involves modulation of early innate proinflammatory cytokine production from liver pDCs and NK cells and subsequent control of MCMV replication and pathology before activation of an adaptive immune response. Altogether, these results highlight a process of virus recognition with multiple pathways in place to promote host resistance to infection in the liver microenvironment.