ACUTE VIRULENCE IN MICE IS ASSOCIATED WITH MARKERS ON CHROMOSOME-VIIIIN TOXOPLASMA-GONDII

Toxoplasma gondii has an unusual population structure consisting of th ree widely distributed clonal lineages. Acute virulence in mice is str ictly observed in type I strains, indicating that a genetic determinan t(s) unique to this lineage controls acute pathogenesis, We have analy zed several naturally occurring recombinant strains of T, gondii that carry allele 1 at the SAG1 locus; this allele is characteristic of the type I strains and was previously found to be 100% correlated with th e acute virulence phenotype. Recombinant strains G622-M and ROD both h ad a predominantly type III genotype, with the significant exception o f allele 1 at the SAG1 locus. Although these two strains had virtually identical multilocus genotypes, they differed in their virulence in m ice. Strain ROD was virulent whereas strain G622-M was nonvirulent, th us demonstrating that the presence of allele 1 at SAG1 is not alone su fficient to confer acute virulence, Several sequence polymorphisms ups tream of SAG1 were found to be highly correlated with the acutely viru lent lineages. Collectively, these results suggest that acute virulenc e is regulated by a region linked to the SAG1 locus on chromosome VIII in T. gondii.