Rabies virus is taken up by neurons, transported to the cell body where replication takes place, and transferred to other neurons transynaptically. Thus, rabies virus represents a useful marker to study membrane traffic and targeting in neurons. Rabies virus and markers for endosomes and other subcellular compartments are colocalized by immunofluorescence and the transport of rabies is being investigated by electron microscopy. It has been determined that shortly after entry, rabies virus is located in endosomes, some of which are acidified. In another series of studies, we are investigating whether the nicotinic acetylcholine receptor serves as a host cell receptor for rabies virus.
Nicotinic receptors are present at the neuromuscular junction and in central nervous system neurons.
Studies are underway to determine if transfection of a non-permissive cell with acetylcholine receptor subunits confers susceptibility to infection. Studies are planned on the interaction of rabies virus with central nicotinic receptors. It will be determined whether cholinergic ligands prevent infection of cells by blocking the virus-receptor interaction. Other puncta contain either rabies virus or dextran. A glial cell underlying the neuron shows fluorescence for dextran but not rabies.