Hydrocephalus in weanling mice induced by a temperature-sensitive mutant of vesicular stomatitis virus

Abstract

Hydrocephalus developed in weanling Swiss-Webster mice after intracerebral (IC) inoculation of a naturally selected temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV). This spontaneous ts mutant was isolated from a persistent infection (pi) of mouse L cells with VSV, and named VSV-tspi 364 (complementation Group I). High doses of the mutant virus induced hydrocephalus in 87% of the mice. Infected mice were clinically asymptomatic, except for a few with transient hind-limb paralysis and proximal muscle weakness. After inoculation, mice were killed every other day for the first two weeks, and weekly thereafter for two months. Virological studies showed replication in the brain in the first nine days post-inoculation (DPI). Neutralizing antibody titers increased rapidly after 15 DPI, and elevated titers were measured at 30 DPI. Pathologically, there was patchy ependymal cell necrosis in the aqueduct and lateral ventricles, as early as the second DPI. Mild meningoencephalitis and severe ependymal cell necrosis with focal aqueductal stenosis were present iun the first two weeks of infection. Hydrocephalus began as early as 10 DPI and became severe at 28 DPI. This represents the first animal model for hydrocephalus following IC inoculation of a spontaneous ts mutant of a rhabdovirus. In our study, inoculation of mice with wild-type VSV and with other spontaneous and chemical ts mutants of VSV IC as well as with tspi 364 by other routes did not cause hydrocephalus.