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Apolipoprotein L-I is the trypanosome lytic factor of human serum

Nature volume 422, pages 83–87 (2003)Cite this article

Abstract

Human sleeping sickness in east Africa is caused by the parasite Trypanosoma brucei rhodesiense. The basis of this pathology is the resistance of these parasites to lysis by normal human serum (NHS)1,2 . Resistance to NHS is conferred by a gene that encodes a truncated form of the variant surface glycoprotein termed serum resistance associated protein (SRA)3,4 . We show that SRA is a lysosomal protein, and that the amino-terminal α-helix of SRA is responsible for resistance to NHS. This domain interacts strongly with a carboxy-terminal α-helix of the human-specific serum protein apolipoprotein L-I (apoL-I). Depleting NHS of apoL-I, by incubation with SRA or anti-apoL-I, led to the complete loss of trypanolytic activity. Addition of native or recombinant apoL-I either to apoL-I-depleted NHS or to fetal calf serum induced lysis of NHS-sensitive, but not NHS-resistant, trypanosomes. Confocal microscopy demonstrated that apoL-I is taken up through the endocytic pathway into the lysosome. We propose that apoL-I is the trypanosome lytic factor of NHS, and that SRA confers resistance to lysis by interaction with apoL-I in the lysosome.

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Figure 1: Expression of SRA and phenotype of pTSARib-transfected T. b. brucei.
Figure 2: Localization of SRA and apoL-I in the T. b. rhodesiense ETat 1.2R clone.
Figure 3: Binding of apoL-I to SRA.
Figure 4: Lytic activity of apoL-I.

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Acknowledgements

We thank M. Chamekh for the pQ30-SRA plasmid, A. Michel and V. Stroobant for peptide synthesis, S. Kler and C. Flore for technical assistance, and D. Perez-Morza and S. Schurmans for help. This work was supported by the Belgian Fund for Scientific Research (FRSM, FWO and Crédit aux Chercheurs) and by the Interuniversity Attraction Poles Programme, Belgian State, Federal Office for Scientific, Technical and Cultural Affairs. R.B., L.V. and L.L. are, respectively, Research Director and Research Associates at the Belgian Fund for Scientific Research.

Author information

Author notes

  1. Derek P. Nolan

    Present address: Department of Biochemistry, Trinity College, Dublin, 2, Ireland

  2. Luc Vanhamme, Françoise Paturiaux-Hanocq, Philippe Poelvoorde and John P. Kane: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Molecular Parasitology, IBMM, University of Brussels, 12, rue des Profs Jeener et Brachet, B6041, Gosselies, Belgium

    Luc Vanhamme, Françoise Paturiaux-Hanocq, Philippe Poelvoorde, Derek P. Nolan, Annette Pays, Patricia Tebabi & Etienne Pays

  2. Centre de Biophysique Moléculaire Numérique, University of Gembloux, B5030, Belgium

    Laurence Lins & Robert Brasseur

  3. Department of Parasitology, Institute for Tropical Medicine, Antwerp, B2000, Belgium

    Jan Van Den Abbeele

  4. Laboratory of Cellular Immunology, Free University of Brussels, Sint Genesius Rode, B1640, Belgium

    Huang Van Xong & Patrick De Baetselier

  5. Laboratory of Applied Genetics, IBMM, University of Brussels, B6041, Belgium

    Alain Jacquet & Nicole Moguilevsky

  6. Unit of Cellular Biochemistry & Biology, University of Namur, B5000, Belgium

    Marc Dieu & Marc Dieu

  7. Cardiovascular Research Institute, University of California, San Francisco, California, 94143-0130, USA

    John P. Kane

Authors
  1. Luc Vanhamme
  2. Françoise Paturiaux-Hanocq
  3. Philippe Poelvoorde
  4. Derek P. Nolan
  5. Laurence Lins
  6. Jan Van Den Abbeele
  7. Annette Pays
  8. Patricia Tebabi
  9. Huang Van Xong
  10. Alain Jacquet
  11. Nicole Moguilevsky
  12. Marc Dieu
  13. John P. Kane
  14. Patrick De Baetselier
  15. Robert Brasseur
  16. Etienne Pays

Corresponding author

Correspondence to Etienne Pays.

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Competing interests

The authors declare that they have no competing financial interests.

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Cite this article

Vanhamme, L., Paturiaux-Hanocq, F., Poelvoorde, P. et al. Apolipoprotein L-I is the trypanosome lytic factor of human serum. Nature 422, 83–87 (2003). https://doi.org/10.1038/nature01461

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