Interferon-γ-mediated site-specific clearance of alphavirus from CNS neurons

Recovery from viral encephalomyelitis requires immune-mediated noncytolytic clearance from neurons by mechanisms assumed to be the same for all neurons. In alphavirus encephalomyelitis, antibody clears infectious virus from neurons in all regions of the central nervous system (CNS), but CD8 T cells contribute to elimination of viral RNA. To understand the role of T cells in clearance, we infected antibody knockout mice with Sindbis virus. Virus was cleared from spinal cord and brain stem neurons, but not from cortical neurons, and required both CD4 and CD8 T cells. Infection with cytokine-expressing recombinant viruses suggested that T cells used interferon-gamma, but not tumor necrosis factor alpha, in clearing virus and that populations of neurons differ in responsiveness to this effector pathway.