Mouse Moloney leukemia virus infects microglia but not neurons even though it induces motor neuron disease.

Motor neuron degeneration caused by ts1 MoMuLV occurs by an indirect mechanism and hypothetically appears associated with a two-cell or three-cell pathogenesis hypothesis. The first step in this hypothesis is associated with a small subset of resident microglial cells that serve as the principal target cells for ts1 MoMuLV infection. The second step is likely linked to trophic events, probably mediated by cytokines, that lead to hypertrophy and activation of a substantial number of additional microglial cells (autocrine effect) and adjacent astrocytes (paracrine effect). The third step in this hypothesis appears related to indirect neuronal degeneration mediated by cytotoxins produced by activated microglial cells and astrocytes. In this last step, motor neurons located within these foci of activated microglial cells and astrocytes are 'innocent bystander cells' and degenerate and die due to paracrine effects. The mechanism of motor neuron degeneration is poorly understood but is likely linked to a sequential cascade of trophic factors and cytokines resulting in a final common pathway for motor neuron death involving production of oxidative radicals, excitatory aminoacid neurotransmitter-like substances, prostaglandins, or nitric oxide.