Comparative pathogenesis of rabies and rabies like viruses: infection of the central nervous system and centrifugal spread of virus to peripheral tissues

Aspects in the pathogenesis of rabies and rabies like virus (Mokola, Lagos bat) infections in young hamsters from sites of invasion of the central nervous system to the brain and finally to those tissues infected via centrifugal neural spread were studied by tissue titration and light, immunofluorescent, and electron microscopy. From intramuscular inoculation in the hind limb, virus reached lumbar spinal cord neurons in 60 hours and progressed to the brain very rapidly thereafter. An ascending course of infection was seen through levels of the brain before viral antigen filled nearly all neurons in the terminal stages of the disease. Variations in brain immunofluorescent patterns were related to stage of infection, topographic location, virus strain, and route of inoculation. Electron microscopy confirmed the ubiquitous terminal presence of viral inclusions and virus particles in virtually every brain, spinal cord, and ganglion neuron and the absence of involvement of supportive cells of the central nervous system. Centrifugal neural spread of virus terminally reached the eye (retina and cornea) and peripheral nerve endings associated with hairs (including tactile hairs), intestine, and adrenal medulla, where chromaffin cells were also infected. Of the potential sites for production of infectious oronasal secretions, the many nerve end organs of the mouth (taste buds) and nose (olfactory neuroepithelium) were much more heavily infected than salivary gland epithelium. Extraneural infection also occurred terminally in pancreas, brown adipose tissue, and myocardium. A hypothetical mechanism of viral spread was expanded to include ascending infection within the central nervous system and centrifugal peripheral neural spread: passive intraneuronal movement of subviral entities must be interspersed with active viral replication at cell surfaces such that progeny virus may invade contiguous neurons or move within intercellular spaces to ultimately involve neural elements everywhere in the body.