The pathogenesis of western equine encephalitis virus (W.E.E.) in adult hamsters with special reference to the long and short term effects on the C.N.S. of the attenuated clone 15 variant.

The pathogenesis of the virulent strain of western encephalitis virus was compared with that of the attenuated Clone 15 of the virus. The results of the work showed that the 2 strains replicated equally in the C.N.S. and produced lesions of encephalitis, but whereas in infections with the virulent strain there was 100 per cent mortality, infection with the attenuated strain did not produce signs of disease but gave rise to immunity and protection against challenge with the virulent strain of virus. Differences were also observed in the degree of brain damage and in virus replication curves depending on the route of infection. In Clone 15 the route of infection influenced also the levels of antibody production. Immunosuppression changed the pathological picture of the C.N.S. lesions in that after inoculations with Clone 15, the inflammatory reaction usually prominent in non-immunosuppressed hamsters, was either delayed or partly eliminated, while the degenerative and astrocytic changes became very severe and widespread. At the same time a proportion of immunosuppressed hamsters otherwise resistant succumbed to the infection with the attenuated Clone 15, developed signs of disease and died. Immunosuppressed hamsters infected by the peripheral route with the attenuated strain of virus were not protected against challenge by the i.c. route; on the other hand when such cyclophosphamide treated hamsters were infected with Clone 15 by the i.c. route they became solidly protected against challenge with the virulent strain of W.E.E. virus. After the cessation of the acute lesions of encephalitis, a number of hamsters infected by the attenuated Clone 15 developed subacute or chronic sequelae in the C.N.S., localized in the olfactory cortical regions. These sequelae were found only after i.p., i.d. and respiratory infections but not after i.c. inoculations.