Functional analysis of Plasmodium vivax VIR proteins reveals different subcellular localizations and cytoadherence to the ICAM-1 endothelial receptor
| Autor: | Francisco Javier Galán López, Carmen Fernandez-Becerra, A Razaname, M. T. Ferrer, Maria Bernabeu, Giampietro Corradin, H. A. del Portillo, Lorena Martin-Jaular, Alexander G. Maier |
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| Rok vydání: | 2011 |
| Předmět: |
0303 health sciences
ICAM-1 medicine.diagnostic_test 030231 tropical medicine Immunology Plasmodium vivax Plasmodium falciparum Biology Immunofluorescence biology.organism_classification Subcellular localization Microbiology Molecular biology 3. Good health Cell biology Transport protein 03 medical and health sciences 0302 clinical medicine Virology parasitic diseases medicine Antigenic variation Receptor 030304 developmental biology |
| Zdroj: | Cellular Microbiology. 14:386-400 |
| ISSN: | 1462-5814 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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