C58 AND AKR MICE OF ALL AGES DEVELOP MOTOR-NEURON DISEASE AFTER LACTATE DEHYDROGENASE-ELEVATING VIRUS-INFECTION BUT ONLY IF ANTIVIRAL IMMUNE-RESPONSES ARE BLOCKED BY CHEMICAL OR GENETIC MEANS OR AS A RESULT OFOLD-AGE

Age-dependent poliomyelitis is a paralytic disease of C58 and AKR mice caused by cytocidal infection of anterior horn neurons with neuropath ogenic strains of lactate dehydrogenase-elevating virus (LDV). The mot or neurons are rendered LDV-permissive via an unknown mechanism throug h the expression of ecotropic murine leukemia virus (MuLV) in central nervous system (CNS) glial cells. Only old mice develop paralytic dise ase after LDV infection, but mice 5-6 months old or older can be rende red susceptible by suppression of anti-LDV immune responses by a singl e treatment with cyclophosphamide or X-irradiation before LDV infectio n. Younger mice appeared to be resistant in spite of this immunosuppre sive treatment. The present results confirm that mice as young as 1 mo nth of age possess CNS cells expressing ecotropic MuLV and show that t hese mice are susceptible to paralytic LDV infection provided their an ti-LDV immune responses are blocked for an extended period of time by repeated cyclophosphamide treatments or by a genetic defect. Furthermo re, old mice become naturally susceptible to paralytic LDV infection b ecause of an impaired ability to mount a motor neuron protective anti- LDV immune response.