The trypanolytic factor-mechanism, impacts and applications.
The Trypanosoma brucei subspecies T. brucei brucei is non-human infective due to susceptibility to lysis by trypanolytic factor (TLF) in human serum. Reviewed here are the advances which have revealed apolipoprotein L1 (ApoL1), found in high density lipoprotein, as the lysis-inducing component of TLF, the means of uptake via haptoglobin-related protein receptor and the mechanism of resistance in T. b. rhodesiense via its serum resistance-associated (SRA) protein. The first practical steps to application of these discoveries are now in progress; transgenic animals expressing either baboon or minimally truncated human ApoL1 show resistance to both T. b. brucei and T. b. rhodesiense. This has major implications for treatment and prevention of human and animal African trypanosomiasis.
Wheeler
Richard J
RJ
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK. richard.wheeler@path.ox.ac.uk
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000378:metabolism*; D006242:Haptoglobins / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010215:Papio; D015800:Protozoan Proteins / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000502:physiology*; D016833:Trypanosoma brucei rhodesiense / Q000502:physiology*; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000469:parasitology
C108666:APOL1 protein, human; D000951:Antigens, Neoplasm; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; C058632:HPR protein, human; D006242:Haptoglobins; D008075:Lipoproteins, HDL; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C434063:TLF1 protein, human; C403774:serum resistance associated protein, Trypanosoma brucei