Identification of a Region of PfEMP1 That Mediates Adherence of Plasmodium falciparum Infected Erythrocytes to CD36: Conserved Function With Variant Sequence

Adherence of mature parasitized erythrocytes (PE) of Plasmodium falciparum to microvascular endothelial cells contributes directly to the virulence and pathology of this human malaria. The malarial variant antigen, P falciparum erythrocyte membrane protein 1 (PfEMP1), has been implicated as the PE r...

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Bibliographic Details
Published in:Blood 1997-11, Vol.90 (9), p.3766-3775
Main Authors: Baruch, Dror I., Ma, Xin C., Singh, Hardeep B., Bi, Xiahui, Pasloske, Brittan L., Howard, Russell J.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Biological and medical sciences
Blood Proteins - genetics
Blood Proteins - immunology
CD36 Antigens
Cell Adhesion - immunology
CHO Cells
Cricetinae
Erythrocyte Membrane - immunology
Erythrocytes - cytology
Erythrocytes - immunology
Erythrocytes - parasitology
Fundamental and applied biological sciences. Psychology
Humans
Life cycle. Host-agent relationship. Pathogenesis
Malaria, Falciparum - blood
Molecular Sequence Data
Plasmodium falciparum
Protozoa
Protozoan Proteins - genetics
Protozoan Proteins - immunology
Sequence Alignment
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Summary:Adherence of mature parasitized erythrocytes (PE) of Plasmodium falciparum to microvascular endothelial cells contributes directly to the virulence and pathology of this human malaria. The malarial variant antigen, P falciparum erythrocyte membrane protein 1 (PfEMP1), has been implicated as the PE receptor for CD36 on endothelial cells. We identified the region of PfEMP1 that mediates adherence of PE to CD36 and showed that a recombinant protein fragment from this region blocked and reversed adherence of antigenically different parasites. Sequence variation was evident in the CD36 binding domain of different PfEMP1 genes, yet many highly conserved residues, particularly cysteine residues, are evident. This suggests a highly conserved shape that mediates adherence to CD36. Immunization with the CD36-binding domain elicited sera that are cross-reactive with the different recombinant proteins but are strain-specific for the PE surface. Novel anti-adherence therapeutics and a malaria vaccine may derived from exploitation of the structure of the CD36 binding domain of PfEMP1.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V90.9.3766