Rabies virus infection of myotubes and neurons as elements of the neuromuscular junction.

The neuromuscular junction represents a site of transit for both fixed and street rabies viruses. Infection of cultured rat myotubes by fixed rabies virus was found to be restrictive, and although fluorescence observations showed that cells were infected, there were no infectious virus particles in the supernatant of infected myotubes. In contrast, infection of myotubes with street rabies virus produced infectious virus particles, and kinetic studies noted a growth cycle in these cells. Neurons derived from the rat spinal cord or from dorsal root ganglia were 10-100-fold more susceptible to infection with fixed rabies challenge virus strain (CVS) than were the myotubes, a finding that confirms the basically neurotropic nature of rabies virus. The abortive infection of CVS rabies in muscle cells may be one possible mechanism by which virus persists at the site of inoculation. In addition, competition-binding experiments show that alpha-bungarotoxin at 10(-5)-10(-7) M inhibits rabies virus infection of myotubes, a finding that suggests the involvement of low-affinity nicotinic acetylcholine receptors for rabies virus. Sialic acid was shown to be necessary for the attachment of rabies virus to the myotubes, a requirement confirming earlier data for other cell types. These data confirm observations in vivo. Infection of these cells in primary culture, which represent the natural target for rabies virus, mimics the situation in vivo. Such a model permits further investigation of virus-cell interactions at the neuromuscular junction.