title: Functional analysis of Plasmodium vivax VIR proteins reveals different subcellular localizations and cytoadherence to the ICAM-1 endothelial receptor.
abstract: The subcellular localization and function of variant subtelomeric multigene families in Plasmodium vivax remain vastly unknown. Among them, the vir superfamily is putatively involved in antigenic variation and in mediating adherence to endothelial receptors. In the absence of a continuous in vitro culture system for P. vivax, we have generated P. falciparum transgenic lines expressing VIR proteins to infer location and function. We chose three proteins pertaining to subfamilies A (VIR17), C (VIR14) and D (VIR10), with domains and secondary structures that predictably traffic these proteins to different subcellular compartments. Here, we showed that VIR17 remained inside the parasite and around merozoites, whereas VIR14 and VIR10 were exported to the membrane of infected red blood cells (iRBCs) in an apparent independent pathway of Maurer's clefts. Remarkably, VIR14 was exposed at the surface of iRBCs and mediated adherence to different endothelial receptors expressed in CHO cells under static conditions. Under physiological flow conditions, however, cytoadherence was only observed to ICAM-1, which was the only receptor whose adherence was specifically and significantly inhibited by antibodies against conserved motifs of VIR proteins. Immunofluorescence studies using these antibodies also showed different subcellular localizations of VIR proteins in P. vivax-infected reticulocytes from natural infections. These data suggest that VIR proteins are trafficked to different cellular compartments and functionally demonstrates that VIR proteins can specifically mediate cytoadherence to the ICAM-1 endothelial receptor.
authors: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain.
authors: M
authors: M
authors: Bernabeu
authors: F J
authors: FJ
authors: Lopez
authors: M
authors: M
authors: Ferrer
authors: L
authors: L
authors: Martin-Jaular
authors: A
authors: A
authors: Razaname
authors: G
authors: G
authors: Corradin
authors: A G
authors: AG
authors: Maier
authors: H A
authors: HA
authors: Del Portillo
authors: C
authors: C
authors: Fernandez-Becerra
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D046508:Culture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D017125:Genes, Protozoan; D006790:Host-Parasite Interactions; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D052940:Merozoites / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics; D010966:Plasmodium vivax / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D052939:Schizonts / Q000378:metabolism
chemical_list: C573420:ICAM1 protein, human; D015800:Protozoan Proteins; D018799:Intercellular Adhesion Molecule-1