Rabies and borna disease. A comparative pathogenetic study of two neurovirulent agents.

BACKGROUND

Rabies and Borna disease viruses have been regarded as classical neurotropic agents. Many pathogenetic similarities are shared by these two negative strand RNA viruses. In view of recently gained data on the virology and pathology of these two diseases, and up-to-date comparative pathogenetic study seems to be justified.

EXPERIMENTAL DESIGN

This study is based on a survey of experimental and natural infections of laboratory animals and natural hosts. The morphologic damage to the nervous system has been evaluated by light and electron microscopy, with special emphasis on immunocytochemical methods.

RESULTS

This comparative study disclosed that both viruses are transported inside axons, pass synapses and propagate along neuronal networks. At the sites of synaptic transfer, full virus particles can never be detected in the early phase of rabies virus infection; in Borna disease virus (BDV) infection, virus particles cannot be found in any phase of disease progression. Thus, a major difference exists between the two agents insofar as rabies virus is morphologically well characterized, whereas BDV has never been visualized in tissue sections. Furthermore, rabies virus infects only neurons, whereas BDV also infects glial cells. The host range and the scale of infection of extraneural tissues by both agents is extremely similar.

CONCLUSIONS

These observations allow us to postulate that the synaptic transfer of both viruses likely ensures in the form of bare nucleocapsids (ribonucleoprotein-transcriptase complexes). While in the later phases of replication complete rabies virions are regularly assembled, BDV propagates within the central nervous system in an incomplete form, so that it remains morphologically imperceptible. Thus, BDV may appear in a complete, enveloped form only when exiting the host organism. The dissemination patterns of the two agents may be influenced by specific affinities to neurotransmitter receptor sites. It remains unresolved, why BDV readily infects non-neuronal central nervous system cells, while rabies virus remains restricted to neuronal elements.