[Replication of fixed rabies virus in cellular suspension].
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Biomedical subjects
Publications and source records attributed to H Tsiang.
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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.
RV194-2 rabies virus, an avirulent mutant of CVS strain, induces an inapparent infection limited to the central nervous system (CNS) in adult mice inoculated intracerebrally. This fact suggest that immune response of the host is able to eliminate the virus in CNS. For this reason, we have studied the induction of interferon and the humoral immune responses in BALB/c mice after RV194-2 inoculation. These mice presented high levels of interferon in the plasma and in the brain, with elevated levels of neutralizing antirabies antibodies. The 2-5A synthetase, an enzyme marker of interferon action, was analyzed in the brain of inoculated animals. Its enhancement in parallel to the interferon production in the brain, showed biochemical evidence that this interferon is active. Forty five days after RV194-2 virus inoculation, mice were protected against a challenge with the CVS virulent strain. The results presented herein show that RV194-2 strain has a high level of immunogenicity.
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A human rabies vaccine is prepared on bovine foetal kidney cells in absence of serum. This vaccine is concentrated and purified by zonal centrifugation. An immunogenic vaccine is obtained from the purified viral particles. Preliminary results are reported.