ROLE OF ABORTIVE RETROVIRAL INFECTION OF NEURONS IN SPONGIFORM CNS DEGENERATION

RETROVIRUSES are involved in several human neurological diseases with varying pathological features1-3. Whether these diseases are due to a direct effect of the virus on nervous system cells is unknown. To gain insight into the pathogenesis of one retroviral neurological disease, we are studying the murine neurotropic retro-virus, Cas-Br-E, which causes lower motor neuron disease associated with spongiform degenerative changes in brain and spinal cord4. Central nervous system (CNS) injury seems to be due to direct viral action5, but the precise target cells of the virus are uncertain. After blood-borne virus enters the CNS it is found in capillary endothelial cells5-7. No microscopic evidence for virus within glia or neurons has been found in some studies6, whereas virus or incomplete particles have been observed in CNS cells in other studies5,8. Here we identify the neuron as a major target for Cas-Br-E in the CNS, suggesting that this disease may be a direct result of viral infection of neurons. We also show that envelope protein (Env, encoded by the env gene), a major determinant of neurovirulence9,10, cannot be detected in neurons but is present in non-neuronal cells, although spliced env messenger RNA is synthesized in CNS tissue. This suggests that a post-transcriptional step in Cas-Br-E Env protein synthesis is impaired and that the neurological disease may be a consequence of abortive replication of virus in neurons. This may explain the failure to find neuronal infection in other neurological diseases by conventional methods of virus detection. © 1990 Nature Publishing Group.