<i>Plasmodium falciparum</i> Associated with Severe Childhood Malaria Preferentially Expresses PfEMP1 Encoded by Group A <i>var</i> Genes

DOI PDF 被引用文献3件
  • Anja T.R. Jensen
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,
  • Pamela Magistrado
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,
  • Sarah Sharp
    3Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
  • Louise Joergensen
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,
  • Thomas Lavstsen
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,
  • Antonella Chiucchiuini
    3Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
  • Ali Salanti
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,
  • Lasse S. Vestergaard
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,
  • John P. Lusingu
    4National Institute for Medical Research, Amani, Tanga, Tanzania
  • Rob Hermsen
    5Department of Medical Microbiology, University Medical Center, 6525 GA Nijmegen, Netherlands
  • Robert Sauerwein
    5Department of Medical Microbiology, University Medical Center, 6525 GA Nijmegen, Netherlands
  • Jesper Christensen
    2Department of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen University Hospital, 2200 Copenhagen, Denmark
  • Morten A. Nielsen
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,
  • Lars Hviid
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,
  • Colin Sutherland
    3Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
  • Trine Staalsoe
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,
  • Thor G. Theander
    1Department of Medical Microbiology and Immunology, Centre for Medical Parasitology, Department of Infectious Diseases,

抄録

<jats:p>Parasite-encoded variant surface antigens (VSAs) like the var gene–encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSASM) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSAUM). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSAUM to in vitro–selected sublines expressing VSASM to identify PfEMP1 responsible for the VSASM phenotype. Expression of VSASM was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.</jats:p>

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