MOLECULAR BASIS OF ANTIGENIC VARIATION ON MALARIA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The basic objective of this research is to understand the molecular mechanisms that govern variant antigen gene expression in Plasmodium. Antigenic variation is a fundamental adaptation to evade a host protective immune response and is one of the major factors contributing to the establishment of chronic blood infections. The classic P. knowlesi-rhesus monkey model of malaria is the primary focus of investigations. This simian malaria model is amenable to both in vitro and in vivo studies and unique stable clones of the P. knowlesi H strain expressing distinct SICA (Schizont Infected Cell Agglutination) variant antigen phenotypes after induced sequential switchings can be maintained after numerous in vivo passages (60 generations) in naive rhesus monkeys. These isogenic clonal lines provide a special tool for studies of the cellular and genetic mechanisms underlying clonal antigenic variation. Recently, we have also initiated complementary investigations on malaria variant antigens using the simian malaria, P. coatneyi, since this species has a similar periodicity, and morphological and immunopathophysiological characteristics that are comparable to the most severe human malaria, P. falciparum. Studies this past year have focused on continued genome wide analyses of the SICAvar gene family and studies developing molecular data relating to our hypothesis of post transcriptional gene silencing as a mechanism to control variant antigen gene expression.