VIRULENT AND AVIRULENT STRAINS OF SEMLIKI FOREST VIRUS SHOW SIMILAR CELL TROPISM FOR THE MURINE CENTRAL-NERVOUS-SYSTEM BUT DIFFER IN THE SEVERITY AND RATE OF INDUCTION OF CYTOLYTIC DAMAGE

The pathogenicity of the avirulent, demyelinating A7 strain of Semliki Forest virus (SFV) and the virulent SFV4 strain (derived from an infe ctious clone) for the central nervous system of adult BALB/c mice foll owing intranasal infection was compared. The techniques used included immunocytochemistry using anti-SFV antibody and antibodies to cell mar kers, in situ hybridization (ISH) using a biotinylated cDNA probe spec ific for SFV, and immunocytochemistry/ISH double labelling. Whereas SF V4 was lethal at 4 days post-infection, A 7-infected mice appeared nor mal at all times. Neuronal necrosis in the pyriform cortex was present in both infections, but developed sooner and was more severe followin g infection with SFV4 than with A7. Intact neurons and putative oligod endrocytes contained viral RNA and virus-specific antigen in SFV4 infe cted mice; viral RNA but not virus-specific antigen was detected in si milar cells in A7-infected mice. These results confirm that SFV4 and A 7 share similar cell tropisms for the murine central nervous system, b ut differ in the severity and rate of development of cytolytic damage. Intranasal infection is an efficient monitoring system for studies of the molecular basis of pathogenicity of SFV infection in mice.