Letters to Nature
Nature 422, 83-87 (6 March 2003) | doi:10.1038/nature01461; Received 15 November 2002; Accepted 3 February 2003
Apolipoprotein L-I is the trypanosome lytic factor of human serum
Luc Vanhamme1,2, Françoise Paturiaux-Hanocq1,2, Philippe Poelvoorde1,2, Derek P. Nolan1,3, Laurence Lins4, Jan Van Den Abbeele5, Annette Pays1, Patricia Tebabi1, Huang Van Xong6, Alain Jacquet7, Nicole Moguilevsky7, Marc Dieu8, John P. Kane9, Patrick De Baetselier6, Robert Brasseur4 & Etienne Pays1
- Laboratory of Molecular Parasitology, IBMM, University of Brussels, 12, rue des Profs Jeener et Brachet, B6041 Gosselies, Belgium
- Centre de Biophysique Moléculaire Numérique, University of Gembloux, B5030 Belgium
- Department of Parasitology, Institute for Tropical Medicine, Antwerp, B2000 Belgium
- Laboratory of Cellular Immunology, Free University of Brussels, Sint Genesius Rode, B1640 Belgium
- Laboratory of Applied Genetics, IBMM, University of Brussels, B6041 Belgium
- Unit of Cellular Biochemistry & Biology, University of Namur, B5000 Belgium
- Cardiovascular Research Institute, University of California, San Francisco, California, 94143-0130 USA
- These authors contributed equally to this work
- Present address: Department of Biochemistry, Trinity College, Dublin 2, Ireland.
Correspondence to: Etienne Pays1 Correspondence and requests for materials should be addressed to E.P. (e-mail: Email: epays@ulb.ac.be).
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 
-helix of SRA is responsible for resistance to NHS. This domain interacts strongly with a carboxy-terminal -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.
