A rhoptry-protein-associated mechanism of clonal phenotypic variation in rodent malaria

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The recognition and invasion of host cells are mediated by components of the apical complex of the ookinete, sporozoite and merozoite stages ofparasites. The paired rhoptries (organelles involved in host-cell recognition) in the apical complex contain many proteins of as-yet unknown function. In the rodent malaria agent, a multigene family codes for merozoite rhoptry proteins of relative molecular mass 235,000 (p235 proteins); these proteins are thought to determine the subset of erythrocytes that the parasites invade. Further support for this idea came from the identification of a region in p235 with weak but significant homology to reticulocyte-binding protein-2 of,and the demonstration that at least one p235 member binds to the erythrocyte surface membrane. Here, using single, micromanipulatedparasites, we describe a new mechanism of gene expression by which the merozoites originating from a single schizont each express a distinct member of this multigene family. We propose that this new type of clonal phenotypic variation provides the parasite with a survival strategy in the mammalian host; this strategy contributes to the observed chronicity of malarial infections. This phenomenon is genetically and functionally distinct from classical antigenic variation, which is mediated by themultigene family of.

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Animals Mice, Inbred BALB C Mice Erythrocytes Plasmodium yoelii Malaria Rodent Diseases RNA, Protozoan Protozoan Proteins Polymerase Chain Reaction