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Erythrocyte invasion profiles are associated with a common invasion ligand polymorphism in Senegalese isolates of Plasmodium falciparum

Published online by Cambridge University Press:  07 January 2009

P. M. LANTOS
Affiliation:
Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115USA
A. D. AHOUIDI
Affiliation:
Laboratory of Bacteriology and Virology, Le Dantec Hospital, Dakar BP 7325, Senegal and Laboratory of Parasitology, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, BP 7325Senegal
A. K. BEI
Affiliation:
Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115USA
C. V. JENNINGS
Affiliation:
Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115USA
O. SARR
Affiliation:
Laboratory of Bacteriology and Virology, Le Dantec Hospital, Dakar BP 7325, Senegal and Laboratory of Parasitology, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, BP 7325Senegal
O. NDIR
Affiliation:
Laboratory of Bacteriology and Virology, Le Dantec Hospital, Dakar BP 7325, Senegal and Laboratory of Parasitology, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, BP 7325Senegal
D. F. WIRTH
Affiliation:
Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115USA
S. MBOUP
Affiliation:
Laboratory of Bacteriology and Virology, Le Dantec Hospital, Dakar BP 7325, Senegal and Laboratory of Parasitology, Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, Dakar, BP 7325Senegal
M. T. DURAISINGH*
Affiliation:
Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115USA
*
*Corresponding author: Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. Tel: +1 617 432 2675. Fax: +1 617 436 4766. E-mail: [email protected]

Summary

Plasmodium falciparum parasites use multiple ligand-receptor interactions to invade human erythrocytes. Variant expression levels of members of the PfRh and PfEBA ligand families are associated with the use of different erythrocyte receptors, defining invasion pathways. Here we analyse a major polymorphism, a large sequence deletion in the PfRh2b ligand, and erythrocyte invasion profiles in uncultured Senegalese isolates. Parasites vary considerably in their use of sialic acid-containing and protease-sensitive erythrocyte receptors for invasion. The erythrocyte selectivity index was not related to invasion pathway usage, while parasite multiplication rate was associated with enhanced use of a trypsin-resistant invasion pathway. PfRh2b protein was expressed in all parasite isolates, although the PfRh2b deletion was present in a subset (~68%). Parasites with the PfRh2b deletion were found to preferentially utilize protease-resistant pathways for erythrocyte invasion. Sialic acid-independent invasion is reduced in parasites with the PfRh2b deletion, but only in isolates derived from blood group O patients. Our results suggest a significant role for PfRh2b sequence polymorphism in discriminating between alternative erythrocyte receptors for invasion and as a possible determinant of virulence.

Type
Research Article
Copyright
Copyright © 2009 Cambridge University Press

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