In vivo assembly and maturation of vesicular stomatitis virus.

Previous studies on vesicular stomatitis virus (VSV) maturation in infected cells have utilized in vitro cell cultures. The present study is, to our knowledge, the first in vivo analysis of VSV-cell interaction in the central nervous system of weaning outbred Swiss mice. Intracerebral inoculation of wild-type VSV resulted in rapid viral replication in brain and spinal cord. By immunoflourescence, viral antigens were first seen in ependymal cells of brain and spinal cord and soon thereafter in surrounding neurons. The large anterior horn neurons of spinal cord appeared to be in the most heavily infected. Ultrastructurally, VSV-neuron interaction evolved in three phases. The first phase consisted of viral entry into the cell by fusion and viropexis. The second phase was characterized by nucleocapsid accumulation and resulted in the appearance of large cytoplasmic inclusions. The third phase was maturation and release from the infected cell and was accomplished by viral budding from plasma membranes. Degenerative changes in infected neurons were generally absent. Cells in the area of the central canal seemed to present a different pattern of virus-cell interaction especially at the level of maturation and release. Some of these cells in advanced stages of degeneration showed viral particles free in nucleocapsid material with no virus-membrane association. Viral budding was not observed and, because these cells do eventually die, it is possible that virus was released in the intercellular space at the moment of cellular disruption. These results suggest that VSV-cell interactions may vary depending upon the nature of the infected cells.