INFECTIVITY OF TRYPANOSOMA-CRUZI STRAINS IS ASSOCIATED WITH DIFFERENTIAL EXPRESSION OF SURFACE GLYCOPROTEINS WITH DIFFERENTIAL CA2+ SIGNALING ACTIVITY

Mammalian cell invasion assays, using metacyclic trypomastigotes of Tr ypanosoma cruzi G and CL strains, showed that the CL strain enters tar get cells in several-fold higher numbers as compared with the G strain . Analysis of expression of surface glycoproteins in metacyclic forms of the two strains by iodination, Immunoprecipitation and FACS, reveal ed that gp90, undetectable in the CL strain, is one of the major surfa ce molecules in the G strain, that expression of gp82 is comparable in both strains and that gp35/50 is expressed at lower levels in the CL strain. Purified gp90 and gp35/50 bound more efficiently than gp82 to cultured HeLa cells. However, the intensity of the Ca2+ response trigg ered in HeLa cells by gp82 was significantly higher than that induced by gp35/50 or gp90. Most of the Ca2+ signalling activity of the metacy clic extract towards HeLa cells was due to gp82 and was inhibitable by gp82-specific monoclonal antibody 3F6. Ca2+ mobilization was also tri ggered in metacyclic trypomastigotes by host-cell components; it was m ainly gp82-mediated and more intense in the CL than in the G strain. W e propose that expression of gp90 and gp35/50 at high levels impairs b inding of metacyclic forms to host cells through productive gp82-media ted interaction, which leads to the target-cell and parasite Ca2+ mobi lization required for invasion. Analysis of metacyclic forms of eight additional T. cruzi strains corroborated the inverse correlation betwe en infectivity and expression of gp90 and gp35/50.