UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection

Crane, Meredith J.; Gaddi, Pamela J.; Salazar-Mather, Thais P.

Previous studies have demonstrated resolution of virus-induced liver disease after 5 days of MCMV infection in WT mice [22, 24, 27, 37] . Therefore, given the impaired inflammatory responses observed in the absence of endosomal TLR signaling, liver sections prepared from 3d and WT mice that were uninfected or infected for 3, 5, or 7 days were hematoxylin and eosin (H&E) stained to evaluate pathology. The histological appearance of liver sections from uninfected 3d and WT mice appeared comparable (Fig. 4, A and B ). By day 3 post-MCMV infection, clusters of infiltrating cells or inflammatory foci, which have been shown to coincide with sites of MCMV antigen expression [23, 37] , were present in WT mice and persisted through day 5 before inflammation was resolved by day 7 post-infection (Table 1 , Fig. 4 , C, E and G). While the inflammatory foci per area of liver were equally apparent in liver sections from 3d mice infected for 3 days (Table 1) , there was an increased presence of cytomegalic inclusion bodies characteristic of MCMV-infected cells that were not readily apparent in WT mice (Fig. 4D) . By day 5 postinfection, livers from 3d mice were characterized by widespread areas of inflammation compared to the more punctate foci in WT livers (Fig. 4, E and F) . Moreover, the inflammatory foci per area of liver in 3d mice at day 5 post-infection were significantly more numerous and contained a greater number of nucleated cells compared to WT (Table 1) . However, by day 7 post-infection, inflammation in 3d mice showed signs of resolution that were similar to WT (Table 1, Fig. 4 , G and H).