Viral infection of the central nervous system: from experimental model to human application.

The Daniel's strain of Theiler's virus, a murine picorna virus, induces a n eurological disease characterized by an acute encephalomyelitis, followed b y a persistent infection of the white matter. This late demyelinating disea se is studied as a model for multiple sclerosis because of its chronicity a nd similarity to the histology of the lesions. This mouse model of viral in fection allows a review of the various major aspects of the immune response to an infection of the central nervous system. The observation that inbred strains of mice differ in their susceptibility to the demyelinating diseas e provided the base for genetic studies that were informative for the invol ved functional immunological mechanisms. A locus in the H-2D region of the major histocompatibility complex was shown to control susceptibility to the persistent infection, leading to approach the key role of CTLs. Non-H-2 ge nes were also implicated, one of which was mapped close to the IFN-gamma lo cus on chromosome 10. The key role of IFN-gamma was demonstrated, and led t o a further investigation of the function of the potential producers of thi s cytokine, namely NK, CD8(+), and CD4(+) Th1 cells. Finally, non-immune fa ctors were also shown to play a role in resistance. A personal view of the antiviral immune responses emerged from this review. (C) 1999 Elsevier, Par is.