Infection of the Central Nervous System Produced by Mixtures of Defective-Interfering Particles and Wild-Type Vesicular Stomatitis Virus in Mice

Abstract

In contrast to wild-type vesicular stomatitis virus (VSV), which produces a fulminant illness with death in two to three days, mixtures of homologous defective autointerfering (DI) particles and wild-type VSV (DI-wild-type VSV) injected intracerebrally into mice resulted in a slowly progressive disease of the central nervous system (CNS). In fact, mice inoculated with DI-wild-type VSV survived up to nine days after infection and displayed striking paralysis of the hind limbs. The slowly progressive CNS disease accompanying infection with DI-wild-type VSV was characterized by production of only 1% of the amount of VSV recovered when wild-type VSV was injected alone. Morphologically, mice infected with DI-wild-type VSV displayed a spectrum of pathologic changes not encountered with disease due to wild-type VSV alone. These changes included the presence of parenchymal necrosis in the spinal cord, changes in and secondary demyelination of the white matter, striking leptomeningeal inflammation, and spongiform changes in the gray matter of the neuropil. Since these pathological features are not found when CNS disease results from either wild-type VSV or temperature-sensitive (ts) mutants of VSV, it is suggested that CNS infection with ts VSV is not mediated principally by production of DI particles. Furthermore, in vivo CNS infection with DI-wild-type VSV did not appear to be mediated by production of ts VSV mutants.