Infection of the central nervous system produced by R1 vesicular stomatitis virus

Previous studies of vesicular stomatitis virus infection of the central nervous system in mice have demonstrated that both temperature-sensitive mutants and defective interfering particles produce alterations from wild type disease. To examine further the role of the biologic properties of the virus, we studied the disease produced by R1-vesicular stomatitis virus, a temperature-insensitive revertant derived from the temperature-sensitive T1026 mutant. Whereas wild type produced acute encephalitis and death in 2 to 3 days in BALB/c mice, R1 produced, in contrast, a paralytic disease 5 to 6 days postinoculation and death on days 6 to 7. R1 infection is productive, although with altered kinetics of growth. No alterations of the biologic properties of the virus following intracerebral passage could be detected. The morphologic features showed a striking localization of viral replication and damage to the anterior horns of the spinal cord with sparing of the ependymal cells, unlike the situation in wild type infection. At the time of clinical onset of R1 disease, the morphologic appearances were degenerative in nature. These features correlate with the clinical localization and development of disease. In addition, morphologic evidence for trans-synaptic spread of R1 and wild type has been found. Although the delayed and altered central nervous system disease resembles aspects of delayed disease produced in other situations, it seems clear that the mechanisms operative here are unlike those previously described and may be related to a unique genomic defect in R1 or its interaction with host cell factors.