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PfEMP1, polymorphism and pathogenesis

C I Newbold1, A G Craig, S Kyes

  • 1Molecular Parasitology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, U.K. cinewbold@molbiol.ox.ac.uk

Annals of Tropical Medicine and Parasitology
|July 1, 1997
PubMed
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Plasmodium falciparum causes severe malaria by adhering to endothelial cells, a process mediated by var genes. ICAM-1 binding is strongly linked to cerebral malaria development.

Area of Science:

  • Malariology
  • Molecular Parasitology
  • Immunology

Background:

  • Plasmodium falciparum exhibits higher virulence than other human malaria species.
  • Adherence to endothelial cells and rosette formation are key virulence factors.
  • Sequestration of infected erythrocytes in deep vasculature contributes to severe disease, including cerebral malaria.

Purpose of the Study:

  • To investigate the role of endothelial receptors in Plasmodium falciparum virulence.
  • To identify specific receptors associated with cerebral malaria development.
  • To explore the function of var genes in mediating endothelial adhesion.

Main Methods:

  • Review of laboratory, field, post-mortem, and direct receptor-binding studies.
  • Analysis of identified endothelial receptors (CD36, thrombospondin, ICAM-1, VCAM, E-selectin, chondroitin-4-sulphate).

Related Experiment Videos

  • Examination of var gene products responsible for receptor-specific binding.

    • Main Results:

    • ICAM-1 binding is most strongly associated with cerebral malaria development among identified receptors.
    • The molecule mediating infected erythrocyte adherence is encoded by clonally variable var genes.
    • Progress has been made in defining var-gene regions responsible for specific receptor binding.

    Conclusions:

    • Endothelial receptor utilization, particularly ICAM-1, is a crucial determinant of cerebral malaria.
    • Var genes encode the antigens responsible for Plasmodium falciparum adherence to endothelium.
    • The organization and evolution of var genes are linked to antigenic variation and adhesion functions.