Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice
(A and B) Mx2-Luc reporter mice were i.p. infected with 2 × 104 PFU CVB3 and in vivo imaging was performed (A) at the indicated dpi (n = 3; one representative mouse is shown). (B) 0 and 2 dpi Mx2-Luc reporter mice were perfused with PBS, organs were dissected, homogenates of spleen, cervical lymph nodes (cLN), liver, pancreas, salivary gland, and heart were assessed for reporter activity in vitro (n = 6). Values are mean + SD. Mann-Whitney test was used for statistical analysis. (C) Mx1, Mx1-IFNAR-/-, Mx1-IFNLR-/-, and Mx1-IFNAR-/-IFNLR-/- mice were infected i.p. with 2 × 104 PFU CVB3 and sacrificed 2 dpi. Immunohistochemical analysis of MX1 expression within sections of liver (line 1) and pancreas (line 2). MX1 positive nuclei of hepatocytes (line 1) or acinar cells (line 2) are highlighted by white and black arrow heads, respectively. Inserts show MX1 immunoreactivity of nuclei of bile ducts (line 1) or pancreatic ducts (line 2). Bars = 10 μm. Representative sections of one mouse out of four are shown. (D) Mx1, Mx1-IFNAR-/-, Mx1-IFNLR-/-, and Mx1-IFNAR-/-IFNLR-/- mice were infected as in (C) and monitored for survival (n = 9–10). *P < 0.05, **P < 0.01, ***P < 0.001, n.s. = not statistically significant.