title: A Primate APOL1 Variant That Kills Trypanosoma brucei gambiense.
abstract: Humans are protected against infection from most African trypanosomes by lipoprotein complexes present in serum that contain the trypanolytic pore-forming protein, Apolipoprotein L1 (APOL1). The human-infective trypanosomes, Trypanosoma brucei rhodesiense in East Africa and T. b. gambiense in West Africa have separately evolved mechanisms that allow them to resist APOL1-mediated lysis and cause human African trypanosomiasis, or sleeping sickness, in man. Recently, APOL1 variants were identified from a subset of Old World monkeys, that are able to lyse East African T. b. rhodesiense, by virtue of C-terminal polymorphisms in the APOL1 protein that hinder that parasite's resistance mechanism. Such variants have been proposed as candidates for developing therapeutic alternatives to the unsatisfactory anti-trypanosomal drugs currently in use. Here we demonstrate the in vitro lytic ability of serum and purified recombinant protein of an APOL1 ortholog from the West African Guinea baboon (Papio papio), which is able to lyse examples of all sub-species of T. brucei including T. b. gambiense group 1 parasites, the most common agent of human African trypanosomiasis. The identification of a variant of APOL1 with trypanolytic ability for both human-infective T. brucei sub-species could be a candidate for universal APOL1-based therapeutic strategies, targeted against all pathogenic African trypanosomes.
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: Anneli
authors: A
authors: Cooper
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: Paul
authors: P
authors: Capewell
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: Caroline
authors: C
authors: Clucas
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: Nicola
authors: N
authors: Veitch
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: William
authors: W
authors: Weir
authors: Department of Medical Parasitology, Langone School of Medicine, New York University, New York, New York, United States of America.
authors: Russell
authors: R
authors: Thomson
authors: Department of Medical Parasitology, Langone School of Medicine, New York University, New York, New York, United States of America.
authors: Jayne
authors: J
authors: Raper
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: Annette
authors: A
authors: MacLeod
mesh_terms: D000351:Africa, Eastern / Q000453:epidemiology; D000354:Africa, Western / Q000453:epidemiology; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D014644:Genetic Variation; D006801:Humans; D048531:Papio papio / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D014347:Trypanosoma brucei gambiense / Q000187:drug effects*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000453:epidemiology / Q000469:parasitology
chemical_list: D001053:Apolipoproteins; D011994:Recombinant Proteins