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Developmental selection of var gene expression in Plasmodium falciparum

Nature volume 394, pages 392–395 (1998)Cite this article

Abstract

The protozoan Plasmodium falciparum causes lethal malaria1. Adhesion of erythrocytes infected with P. falciparum to vascular endothelium and to uninfected red blood cells (rosetting) may be involved in the pathogenesis of severe malaria2,3,4. The binding is mediated by the antigenically variant erythrocyte-membrane-protein-1 (PfEMP-1)5,6,7,8, which is encoded by members of the P. falciparum var gene family9,10. The control of expression and switching of var genes seems to lack resemblance to mechanisms operating in variant gene families of other microbial pathogens11,12. Here we show that multiple, distinct var gene transcripts (about 24 or more) can be detected by reverse transcription and polymerase chain reaction in bulk cultures of the rosetting parasite FCR3S1.2, despite the adhesive homogeneity of the cultures. We also detected several var transcripts in single erythrocytes infected with a ring-stage parasite of FCR3S1.2, and found that different var genes are transcribed simultaneously from several chromosomes in the same cell. In contrast, we detected only one var transcript, FCR3S1.2 var-1, which encodes the rosetting PfEMP-1 protein13, in individual rosette-adhesive trophozoite-infected cells, and we found only one PfEMP-1 type at the erythrocyte surface by labelling with 125iodine and immunoprecipitation. We conclude that a single P. falciparum parasite simultaneously transcribes multiple var genes but, through a developmentally regulated process, selects only one PfEMP-1 to reach the surface of the host cell.

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Figure 1: General structure of var/PfEMP-1.
Figure 2: Predicted amino-acid sequences of var transcripts from bulk cultured FCR3S12.
Figure 3: Identification of var transcripts in single Falciparum parasites at the ring stage.
Figure 4: Chromosomal hybridization of var genes simultaneously expressed in individual parasites.
Figure 5: One PfEMP-1 type is expressed on the surface of the trophozoite-infected erythrocyte.
Figure 6: Outline of the activation and selection of var genes, and subsequent expression of PfEMP-1 during the intra-erythrocyticphase of asexual P. falciparum.

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Acknowledgements

We thank K. Berzins for the gift of malaria immune sera. These studies were supported by grants from the Swedish Medical Research Council and the Karolinska Institutet.

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Author notes

  1. Qijun Chen, Victor Fernandez and Santanu Datta: These authors contributed equally to this work.

Authors and Affiliations

  1. Microbiology and Tumor Biology Center, Karolinska Institutet and the Swedish Institute for Infectious Disease Control, Box 280, Stockholm, S-171 77, Sweden

    Qijun Chen, Victor Fernandez, Annika Sundström, Annika Sundström, Martha Schlichtherle, Per Hagblom & Mats Wahlgren

  2. Changchun University of Agriculture and Animal Sciences, 175 Xi An Da Lu, Changchun, 130062, People's Republic of China

    Qijun Chen

  3. Astra Research Centre, P.B. 359, Malleswaram, Bangalore, India

    Santanu Datta

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  1. Qijun Chen
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Correspondence to Mats Wahlgren.

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Chen, Q., Fernandez, V., Sundström, A. et al. Developmental selection of var gene expression in Plasmodium falciparum. Nature 394, 392–395 (1998). https://doi.org/10.1038/28660

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