View the Current Issue

Article

  • The EMBO Journal (1998) 17, 5418 - 5426
  • doi:10.1093/emboj/17.18.5418

Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum

A. Scherf1, R. Hernandez-Rivas2, P. Buffet1, E. Bottius1, C. Benatar1, B. Pouvelle3, J. Gysin3 and M. Lanzer4

  1. Unité de Biologie des Interactions Hôte-Parasite, CNRS URA 1960, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France
  2. Present address: CINVESTAV-IPN, Mexico
  3. Unité de Parasitologie Expérimentale, Faculté de Médecine de la Timone Université de la Méditerranée, Aix–Marseille II, 13385, Marseille, France
  4. Zentrum für Infektionsforschung der Universität Würzburg, D97070 Würzburg, Germany

Correspondence to:

A. Scherf, E-mail: ascherf@pasteur.fr

Received 18 June 1998; Accepted 20 July 1998; Revised 20 July 1998

Members of the Plasmodium falciparum var gene family encode clonally variant adhesins, which play an important role in the pathogenicity of tropical malaria. Here we employ a selective panning protocol to generate isogenic P.falciparum populations with defined adhesive phenotypes for CD36, ICAM-1 and CSA, expressing single and distinct var gene variants. This technique has established the framework for examining var gene expression, its regulation and switching. It was found that var gene switching occurs in situ. Ubiquitous transcription of all var gene variants appears to occur in early ring stages. However, var gene expression is tightly regulated in trophozoites and is exerted through a silencing mechanism. Transcriptional control is mutually exclusive in parasites that express defined adhesive phenotypes. In situ var gene switching is apparently mediated at the level of transcriptional initiation, as demonstrated by nuclear run-on analyses. Our results suggest that an epigenetic mechanism(s) is involved in var gene regulation.

  • Keywords:

    • allelic exclusion,
    • antigenic variation,
    • in situ activation,
    • silencing,
    • var genes