Reovirus replicates extensively in epithelial cells of intestine and biliary tract and induces fatal liver disease in suckling mice lacking functional IFN-λ receptors.

Abstract

<p>Suckling wild-type (n = 7), <i>Ifnar1</i><sup><i>-/-</i></sup> (n = 8) and <i>Ifnlr1</i><sup><i>-/-</i></sup> (n = 11) mice were infected orally with 5 x 10<sup>6</sup> pfu of reovirus T3D. Data from two independent experiments were pooled. (A) Reovirus titers in the small intestine on day 4 post-infection. (B) Immunostaining of small intestinal tissue at day 4 post-infection for reovirus antigen (green), E-cadherin (red) and DAPI (blue). (C) Survival kinetics of wild-type (n = 11), <i>Ifnar1</i><sup><i>-/-</i></sup> (n = 13) and <i>Ifnlr1</i><sup><i>-/-</i></sup> (n = 15) mice. (D) Immunostaining of liver tissue harvested on day 4 post-infection. Reovirus antigen (green), cytokeratin (red) and DAPI (blue). Arrows point to intrahepatic bile ducts. (E) Immunostaining of extrahepatic bile ducts for reovirus antigen (green), cytokeratin (red) and DAPI (blue) at day 4 post-infection. (F) Immunostaining for reovirus antigen of an extrahepatic bile duct from a diseased <i>Ifnlr1</i><sup><i>-/-</i></sup> mouse on day 8 post-infection. Note that the duct is filled with material seemingly originating from virus-infected cells. Bar = 100 μm. ** p<0.01, *** p<0.001.</p

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