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.

To further evaluate the effects of endosomal TLR responses on overall liver function, the liver enzyme alanine aminotransferase (ALT) was measured in serum samples from WT and 3d mice that were uninfected or infected with MCMV for 3, 5 or 7 days. Uninfected mice had comparable baseline levels of systemic ALT (Fig. 5 ). By day 3 of infection, similar elevations in ALT levels were detected in both groups. In contrast, by day 5 post-infection, the levels of systemic ALT in 3d mice reached values of 9006400 U/ L and were three-fold higher than the ALT levels measured in WT mice (2706100 U/L; Fig. 5 ), indicating augmented liver disease. In contrast, by day 7 post-infection, 3d mice demonstrated a sharp decline in systemic ALT levels to values of 117663 U/L, which were comparable to ALT levels exhibited in WT mice (108685 U/L). Thus, at this time point of acute infection, both groups of mice exhibited ALT levels near baseline levels, consistent with the resolution of virus-induced liver pathology observed in 3d and WT mice (Fig. 4, G and H; Fig. 5 ). Taken together, these results suggest that in the absence of endosomal TLR signals, there is pronounced liver inflammation accompanied by a transient increase in liver damage during acute MCMV infection.