Spread of wild-type CDV from leptomeningeal vasculature into the CSF. Brain sections from rCDVSHEGFP(6)-infected (A, B, E, and F) (17 d.p.i.), rCDVSHdTom(6)-infected (14 d.p.i.) (C), and CDVR252-infected (30 d.p.i.) ferrets were analyzed for endothelial cell infection and/or leukocyte trafficking across the walls of meningeal blood vessels in the subarachnoid space. (A and B) Serial H&E-stained (A) and immunohistochemically stained (B) sections of a meningeal blood vessel. The asterisk in the inset of panel A indicates the position of this blood vessel in relation to surrounding brain tissue. (B) Virus infection is visible in endothelial cells (arrowheads), with CDV-infected cells present within the lumen (arrow i), attached to the wall (arrow ii and inset), and transmigrating across the wall of the blood vessel (arrow iii) and in the adjacent subarachnoid space (arrow iv). Bar, 50 μm (A and B). (C) Numerous infected leukocytes present in the subarachnoid space of the meninges. bp, brain parenchyma; ac, arachnoid; pa, pia mater. Bar, 60 μm. (D) Serial H&E-stained (left) and CDV N immunohistochemically stained (right) sections showing an absence of inflammation and virus infection in the meninges in a CDVR252-infected animal. (E) Serial H&E-stained (left) and CDV N immunohistochemically stained (right) sections showing that thickening and inflammation of the meninges are associated with rCDVSHEGFP(6) infection. Bar, 100 μm (D and E). (F) Higher magnification of boxed area in panel D (H&E staining) showing infiltration of myeloid cells (arrows) into the subarachnoid space. Bar, 25 μm.