Sleeping sickness foe unmasked

How trypanosomes evade immune responses and become infective.

Mar 6, 2003
Andrea Rinaldi(

Human sleeping sickness — African trypanosomiasis — is caused by the protozoan parasite Trypanosoma bruceirhodesiense and is transmitted to humans through the bite of infected tsetse flies. Human serum contains a trypanosome lytic factor that can prevent infection by susceptible trypanosomes. Some T. b. rhodesiense strains exhibit resistance to this factor mediated by a gene encoding a truncated form of the variant surface glycoprotein serum resistance associated protein (SRA), but the exact molecular mechanisms behind this resistance have been unclear. In the March 6 Nature, Luc Vanhamme and colleagues at the University of Brussels, Belgium, reveal how the parasite overcomes natural human defenses (Nature, 422:83-87, March 6, 2003).

Vanhamme et al. localized SRA to the lysosome and identified the human-specific serum protein apoL-I — an apolipoprotein associated with high density lipoprotein — as the human trypanolytic factor. The amino-terminal α-helix of SRA bound to a carboxy-terminal α-helix of apoL-I, and disabled its lytic function. ApoL-I observed to enter parasite cells via the endocytic pathway and co-localized with SRA in the lysosome, where the two proteins subsequently interacted.

Blocking the SAR-apoL-I interaction may help to prevent or treat the disease. "This works opens the way for the characterization of peptides that would be useful for both therapy of sleeping sickness due to Trypanosoma bruceirhodesiense and prevention of nagana in cattle," suggest the authors.