[Molecular and cellular aspects of the pathogenesis of rabies]

The true causes of the beginning of the symptoms and the eventual mortality of rabies are not very well known. Immunopathological factors certainly intervene, but they only complete a process of neuronal alteration. Contrary to other viruses which lyse the infected cells, the rabies virus does not necessarily destroy the neurones which are the preferential target cells. On the contrary, RNA synthesis is stimulated during CNS infection by the rabies virus. Synthesis is not stimulated by the multiplication of the rabies virus in the cell lines of fibroblastic or neuronal origin, which suggests the existence of regulations on neuronal level functions in the CNS. Nevertheless, the protein virus synthesis seemed equally submitted to specific neuron regulations or neuronal populations. The traces of a neuronal dysfunction during infection by the rabies virus have been investigated, using as a probe, variations of muscarinic acetyl choline receptors in the CNS. The presence of these receptors is revealed by the use of an antagonistic ligand of acetyl choline, quinuclidinyl benzylate. We were able to show that as regards the rat, the appearance of the first signs of paralysis is correlated with the diminution of the receptor binding. Thus, it seems that the presence of the virus in the CNS provokes neuronal alteration which can in itself condition the viral multiplication and eventually modulate the viral pathogenesis expression.