MAPPING OF A NEUROVIRULENCE DETERMINANT WITHIN THE ENVELOPE PROTEIN OF A POLYTROPIC MURINE RETROVIRUS - INDUCTION OF CENTRAL-NERVOUS-SYSTEMDISEASE BY LOW-LEVELS OF VIRUS

Murine leukemia virus (MuLV) clone Fr98 is a recombinant polytropic vi rus that causes neurological disease characterized by ataxia in suscep tible mouse strains. The envelope gene of Fr98 has been previously sho wn to encode at least two separate neurovirulence determinants. In tie present study, the determinant encoded within the EcoRI/AvrII fragmen t of the envelope gene was further defined. In these experiments, neur ovirulence was associated with a change from a serine to an arginine a t position 195 and a glycine to an alanine at position 198 within the envelope protein. Neurovirulent and nonvirulent virus clones, which di ffered only at these two amino acid residues, showed no difference in the type or location of cells infected. Furthermore, equivalent levels of viral p30 capsid protein were detected in the brains of mice infec ted with either the neurovirulent or nonvirulent virus clones. These r esults were consistent with the interpretation that the envelope prote in of the neurovirulent virus differed from that of the nonvirulent vi rus by having a greater toxic effect on central nervous system functio n.