Semliki Forest virus induced, immune mediated demyelination: the effect of irradiation.

Intraperitoneal infection with the avirulent A7(74) strain of the alphavirus Semliki Forest virus (SFV) induces an immune mediated demyelinating encephalomyelitis. The blood and brain virus titres, the serum antibody titres and the histopathological changes in the brains of normal mice and mice immunosuppressed with 5.0 or 8.0 Gy total body irradiation (TBX) were determined. SFV infection of immunosuppressed mice resulted in persistently high blood and brain virus titres, neuronal pycnosis, paralysis and death. No demyelination or central nervous system (CNS) inflammatory response occurred in these immunosuppressed mice despite high and persistent brain virus titres. The CNS inflammatory response and associated demyelination could be restored to infected immunosuppressed mice by adoptive transfer of spleen cells, and these changes were brought forward if the donor spleen cells were from mice previously sensitized to SFV. The results indicate that the immune response following SFV A7(74) infection is both protective and pathogenic, and that the demyelination is immune mediated and does not result from direct viral destruction of oligodendrocytes, or any other direct effect of the virus.