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

Author

Listed:
  • Luc Vanhamme

    (University of Brussels)

  • Françoise Paturiaux-Hanocq

    (University of Brussels)

  • Philippe Poelvoorde

    (University of Brussels)

  • Derek P. Nolan

    (University of Brussels
    Trinity College)

  • Laurence Lins

    (University of Gembloux)

  • Jan Van Den Abbeele

    (Institute for Tropical Medicine)

  • Annette Pays

    (University of Brussels)

  • Patricia Tebabi

    (University of Brussels)

  • Huang Van Xong

    (Free University of Brussels)

  • Alain Jacquet

    (University of Brussels)

  • Nicole Moguilevsky

    (University of Brussels)

  • Marc Dieu

    (University of Namur)

  • John P. Kane

    (University of California)

  • Patrick De Baetselier

    (Free University of Brussels)

  • Robert Brasseur

    (University of Gembloux)

  • Etienne Pays

    (University of Brussels)

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.

Suggested Citation

  • Luc Vanhamme & Françoise Paturiaux-Hanocq & Philippe Poelvoorde & Derek P. Nolan & Laurence Lins & Jan Van Den Abbeele & Annette Pays & Patricia Tebabi & Huang Van Xong & Alain Jacquet & Nicole Moguil, 2003. "Apolipoprotein L-I is the trypanosome lytic factor of human serum," Nature, Nature, vol. 422(6927), pages 83-87, March.
    • Handle: RePEc:nat:nature:v:422:y:2003:i:6927:d:10.1038_nature01461
    DOI: 10.1038/nature01461
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    Cited by:

    1. Hagen Sülzen & Jakub Began & Arun Dhillon & Sami Kereïche & Petr Pompach & Jitka Votrubova & Farnaz Zahedifard & Adriana Šubrtova & Marie Šafner & Martin Hubalek & Maaike Thompson & Martin Zoltner & S, 2023. "Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Eva Horáková & Laurence Lecordier & Paula Cunha & Roman Sobotka & Piya Changmai & Catharina J. M. Langedijk & Jan Van Den Abbeele & Benoit Vanhollebeke & Julius Lukeš, 2022. "Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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