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Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum
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Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var

Anja T R Jensen1, Pamela Magistrado, Sarah Sharp

  • 1Department of Medical Microbiology and Immunology, The Panum Institute, Building 24-2, Blegdamsvej 3, 2200 Copenhagen, Denmark. atrj@biobase.dk

The Journal of Experimental Medicine
|May 5, 2004
PubMed

Insights

Variant surface antigens (VSAs) in Plasmodium falciparum malaria, specifically PfEMP1, are linked to severe disease. Group A var genes, like PFD1235w/MAL7P1.1, are upregulated in severe malaria and are potential vaccine targets.

Area of Science:

  • Malariology
  • Immunology
  • Molecular Biology

Background:

  • Plasmodium falciparum malaria pathogenesis involves parasite-encoded variant surface antigens (VSAs).
  • VSAs, particularly the PfEMP1 family, mediate antigenic variation and red blood cell cytoadhesion.
  • Severe malaria is associated with a distinct VSA subset (VSA(SM)) compared to uncomplicated malaria (VSA(UM)).

Purpose of the Study:

  • To identify the specific PfEMP1 proteins responsible for the VSA(SM) phenotype associated with severe malaria.
  • To compare var gene transcription between parasites expressing VSA(UM) and VSA(SM).

Main Methods:

  • Comparative analysis of var gene transcription in P. falciparum clone 3D7 (VSA(UM)) and in vitro-selected sublines (VSA(SM)).
  • Identification and characterization of upregulated Group A var genes and their encoded proteins.

Main Results:

  • Expression of VSA(SM) correlated with the upregulation of Group A var genes.
  • The Group A gene PFD1235w/MAL7P1.1 was significantly upregulated and its protein product expressed on the infected RBC surface.
  • Group A var gene products, including PFD1235w/MAL7P1.1, are implicated in severe malaria pathogenesis.

Conclusions:

  • Group A var genes encode PfEMP1 proteins crucial for the VSA(SM) phenotype and severe malaria.
  • PFD1235w/MAL7P1.1 is a key candidate for a malaria vaccine targeting severe P. falciparum infections.

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