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Infection and Immunity, July 2007, p. 3531-3538, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00122-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Molecular Analysis of Erythrocyte Invasion in Plasmodium falciparum Isolates from Senegal ^,

Cameron V. Jennings,^1,2, Ambroise D. Ahouidi,^1,2, Martine Zilversmit,³ Amy K. Bei,¹ Julian Rayner,⁴ Ousmane Sarr,² Omar Ndir,² Dyann F. Wirth,¹ Souleymane Mboup,² and Manoj T. Duraisingh^1,2*

Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115,¹ Laboratory of Bacteriology and Virology, Le Dantec Hospital, and Laboratory of Parasitology, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar BP 7325, Senegal,² Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138,³ William C. Gorgas Center for Geographic Medicine, 845 19th St. South, University of Alabama, Birmingham, Alabama 35209⁴

Received 24 January 2007/ Returned for modification 23 February 2007/ Accepted 23 April 2007

The human malaria parasite, Plasmodium falciparum, utilizes multiple ligand-receptor interactions for the invasion of human erythrocytes. Members of the reticulocyte binding protein homolog (PfRh) family have been shown to be critical for directing parasites to alternative erythrocyte receptors that define invasion pathways. Recent studies have identified gene amplification, sequence polymorphism, and variant expression of PfRh paralogs as mechanisms underlying discrimination between pathways for invasion. In this study, we find considerable heterogeneity in the invasion profiles of clonal, uncultured P. falciparum parasite isolates from a low-transmission area in Senegal. Molecular analyses revealed minimal variation in protein expression levels of the PfRh ligands, PfRh1, PfRh2a, and PfRh2b, and an absence of gene amplification in these isolates. However, significant sequence polymorphism was found within repeat regions of PfRh1, PfRh2a, and PfRh2b. Furthermore, we identified a large sequence deletion (0.58 kb) in the C-terminal region of the PfRh2b gene at a high prevalence in this population. In contrast to findings of earlier studies, we found no associations between specific sequence variants and distinct invasion pathways. Overall these data highlight the importance of region-specific elaborations in PfRh sequence and expression polymorphisms, which has important implications in our understanding of how the malaria parasite responds to polymorphisms in erythrocyte receptors and/or evades the immune system.

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* Corresponding author. Mailing address: Harvard School of Public Health, 665 Huntington Avenue, Boston MA, 02115. Fax: (617) 436-4766. Phone: (617) 432-2675. E-mail: mduraisi{at}hsph.harvard.edu

Published ahead of print on 30 April 2007.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: W. A. Petri, Jr.

These authors contributed equally to this work.

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Infection and Immunity, July 2007, p. 3531-3538, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00122-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.