IDENTIFICATION OF THE INFECTED TARGET-CELL TYPE IN SPONGIFORM MYELOENCEPHALOPATHY INDUCED BY THE NEUROTROPIC CAS-BR-E MURINE LEUKEMIA-VIRUS

The Cas-Br-E murine leukemia virus (MuLV) induces a progressive hindli mb paralysis accompanied by a spongiform myeloencephalopathy in suscep tible mice. In order to better understand the pathological process lea ding to these neurodegenerative lesions, we have investigated the natu re of the cell type(s) infected by the virus during the course of the disease in CFW/D and SWR/J mice. For this purpose, we used in situ hyb ridization with virus-specific probes in combination with cell-type-sp ecific histochemical (lectin) and immunological markers as well as mor phological assessment. In the early stage of infection, endothelial ce lls represented the main cell type expressing viral RNA in the central nervous system (CNS). With disease progression and the appearance of lesions, microglial cells became the major cell type infected, account ing for up to 65% of the total infected cell population in diseased ar eas. Morphologically, these cells appeared activated and were frequent ly found in clusters. Infection and activation of microglial cells wer e almost exclusively restricted to diseased regions of the CNS. Neuron s in diseased regions were not discernibly infected with virus at eith er early or late times of disease progression. Similarly, the proporti on of infected astrocytes was typically < 1%. Although some endothelia l cells and oligodendrocytes were infected by the virus, their infecti on was not limited to diseased CNS regions. These results are consiste nt with a model of indirect motor neuron degeneration, subsequent to t he infection of nonneuronal CNS cells and especially of microglial cel ls. Infected microglial cells may play a role in the disease process b y releasing not only virions or viral env-gene-encoded gp70 proteins b ut also other factors which may be directly or indirectly toxic to neu rons. Parallels between microglial cell infection by MuLV and by lenti viruses, and specifically by human immunodeficiency virus, are discuss ed.