Role of abortive retroviral infection of neurons in spongiform CNS degeneration

Abstract

RETROVIRUSES are involved in several human neurological diseases with varying pathological features^1–3. 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 cells^5–7. 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 studies^5,8. 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 neurovirulence^9,10, 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.