Genetics of resistance to the African trypanosomes. II. Differences in virulence associated with VSSA expression among clones of Trypanosoma rhodesiense.

Abstract

C57BL/10SnJ mice were infected with clone LouTat 1.0 of Trypanosoma rhodesiense, and trypanosomes expressing distinct variant specific surface antigens (VSSA) were subsequently isolated and cloned from the blood of a chronically infected mouse at various times during infection. The survival times and parasitaemias of mice infected with these clones were compared to mice infected with the parent clone, LouTat 1.0. Two clones isolated from the terminal parasitaemic peak (LouTat 1.4 and 1.5) were more virulent than LouTat 1.0 and these clones differed from LouTat 1.0 in VSSA expression. These clones caused infections characterized by high parasitaemias and a mean survival time (MST) approximately half that of mice infected with LouTat 1.0. Another distinct clone (LouTat 1.3), isolated at an intermediate time in infection with LouTat 1.0, exhibited intermediate virulence characterized by a MST approximately three-fourths that of the parent clone. The biologic bases for the demonstrated differences in virulence were examined. All clones exhibited no difference in their growth rates, degree of pleomorphism, immunogenicity of VSSA or variant antigenic types (VAT)-specific immune clearance, or in ability to produce antigen nonspecific immunosuppression. However, even though trypanosome-specific immunosuppression occurred after infection with clones of high and low virulence, the more virulent clone exhibited more pronounced suppression. Thus, different VAT arising during a chronic infection with T. rhodesiensis exhibited major differences in their effect on host survival. The detectable biologic differences associated with increased virulence were VSSA expression and induction of parasite-specific immunosuppression. [AS]