Although neuronal virus infection per se is necessary for, and contributes directly to, neuronal dysfunction, the inflammatory response in the CNS is also a major contributor to neuronal damage and can even result in death of nearby uninfected neurons ( Figure 1 ) [19, 20] . The CNS inflammatory response to virus infection consists of activation and proliferation of resident astrocytes and microglial cells and of perivascular and parenchymal infiltration of activated monocytes and lymphocytes from the blood. The mechanism(s) by which the immune response causes neuronal damage are incompletely understood, but evidence exists for production of neurotoxins and reactive oxygen and nitrogen species by activated glial cells, increased levels of the excitotoxic neurotransmitter glutamate, and production of cytokines by activated lymphocytes [21] . The ability to control inflammation through induction of regulatory T cells and suppression of lymphocyte function by infected neurons can be an important determinant of outcome [22, 23] . In alphavirus encephalomyelitis, combined prevention of inflammation and glutamate excitotoxic- ity by treatment with glutamate receptor antagonists prevents paralysis and death despite continued virus replication [20] .