Immunohistochemical localization of neurotropic ecotropic murine leukemia virus in moribund mice

The CasBrE strain of neurotropic ecotropic murine leukemia virus (NE-MuLV) infects susceptible mice and induces a noninflammatory, slowly degenerative nervous system disease. We employed immunohistochemistry to identify which cells in the nervous system and other tissues contained viral antigen in the chronically infected mouse. Rabbit antiserum to the virus was prepared using different combinations of whole virus and synthetic peptides corresponding to a 14-amino-acid sequence of the viral envelope protein. Twenty-four of forty-four (55%) mice neonates inoculated intracranially with NE-MuLV developed symptoms ranging from tremulousness to hindlimb paralysis within 3-9 months. They were subsequently sacrificed and their tissues used for histology and immunohistochemistry. The major locations of viral antigen outside of the central nervous system (CNS) were skeletal muscle and spleen. Skeletal muscle was the only non-nervous system tissue that exhibited degenerative changes as atrophy of viral antigen-bearing oxidative myofibers. In the CNS, viral antigen was detected in neurons, endothelium, and glial cells. Immunohistochemical double-labeling studies for viral antigen and the astrocytic marker glial acidic fibrillary protein (GFAP) demonstrated that the viral antigen-containing glia were oligodendrocytes and not astrocytes. Tissue damage in the brain consisted of vacuolar changes and gliosis principally in the brainstem. Viral antigen was most abundantly localized in these regions of pathologic change. In the spinal cord a different pattern was observed. Although tissue damage was observed throughout the cord, viral antigen was located at the border of the gray and white matter. These findings indicate direct and indirect virus-mediated mechanisms of damage to the CNS.