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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
An in vivo and in vitro model of Plasmodium falciparum rosetting and autoagglutination mediated by varO, a group A var gene encoding a frequent serotype
Infection and Immunity, Volume 76, No. 12, Year 2008
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Description
In the Saimiri sciureus monkey, erythrocytes infected with the varO antigenic variant of the Plasmodium falciparum Palo Alto 89F5 clone bind uninfected red blood cells (rosetting), form autoagglutinates, and have a high multiplication rate, three phenotypic characteristics that are associated with severe malaria in human patients. We report here that varO parasites express a var gene having the characteristics of group A var genes, and we show that the varO Duffy binding-like 1α1 (DBL1α1) domain is implicated in the rosetting of both S. sciureus and human erythrocytes. The soluble varO N-terminal sequence (NTS)-DBL1α1 recombinant domain, produced in a baculovirus-insect cell system, induced high titers of antibodies that reacted with varO-infected red blood cells and disrupted varO rosettes. varO parasites were culture adapted in vitro using human erythrocytes. They formed rosettes and autoagglutinates, and they had the same surface serotype and expressed the same varO gene as the monkey-propagated parasites. To develop an in vitro model with highly homogeneous varO parasites, rosette purification was combined with positive selection by panning with a varO NTS-DBL1α1-specific mouse monoclonal antibody. The single-variant, clonal parasites were used to analyze seroprevalence for varO at the village level in a setting where malaria is holoendemic (Dielmo, Senegal). We found 93.6% (95% confidence interval, 89.7 to 96.4%) seroprevalence for varO surface-reacting antibodies and 86.7% (95% confidence interval, 82.8 to 91.6%) seroprevalence for the recombinant NTS-DBL1α1 domain, and virtually all permanent residents had seroconverted by the age of 5 years. These data imply that the varO model is a relevant in vivo and in vitro model for rosetting and autoagglutination that can be used for rational development of vaccine candidates and therapeutic strategies aimed at preventing malaria pathology. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Vigan-Womas, Inès
France, Paris
Cnrs Centre National de la Recherche Scientifique
Guillotte, Micheline
France, Paris
Cnrs Centre National de la Recherche Scientifique
Le Scanf, Cécile
French Guiana, Cayenne
Institut Pasteur de la Guyane
Igonet, Sébastien
France, Paris
Cnrs Centre National de la Recherche Scientifique
Pêtres, Stéphane
France, Paris
Institut Pasteur, Paris
Juillerat, Alexandre
France, Paris
Cnrs Centre National de la Recherche Scientifique
Badaut, Cyril
France, Paris
Cnrs Centre National de la Recherche Scientifique
Nato, Farida
France, Paris
Institut Pasteur, Paris
Schneider, Achim
France, Paris
Cnrs Centre National de la Recherche Scientifique
Lavergne, Anne
French Guiana, Cayenne
Institut Pasteur de la Guyane
Contamin, Hugues
French Guiana, Cayenne
Institut Pasteur de la Guyane
Tall, Adama
Senegal, Dakar
Institut Pasteur de Dakar
Baril, Laurence
Senegal, Dakar
Institut Pasteur de Dakar
Bentley, Graham Arthur
France, Paris
Cnrs Centre National de la Recherche Scientifique
Mercereau-Puijalon, Odile
France, Paris
Cnrs Centre National de la Recherche Scientifique
Statistics
Citations: 79
Authors: 15
Affiliations: 4
Identifiers
Doi:
10.1128/IAI.00901-08
ISSN:
00199567
Research Areas
Genetics And Genomics
Infectious Diseases
Study Locations
Senegal