Apolipoprotein L1 Variant Associated with Increased Susceptibility to Trypanosome Infection

摘要: ABSTRACT African trypanosomes, except Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense , which cause human trypanosomiasis, are lysed by the serum protein apolipoprotein L1 (ApoL1). These two subspecies can resist ApoL1 because they express resistance proteins T. b. glycoprotein (TgsGP) resistance-associated (SRA), respectively. Whereas in T. b. rhodesiense SRA is necessary sufficient to inhibit ApoL1, T. b. gambiense TgsGP cannot protect against high uptake, so different additional mechanisms contribute limit this uptake. Here we report a complex interplay between trypanosomes an variant, revealing important insights into innate immunity these parasites. Using whole-genome sequencing, characterized atypical infection patient Ghana. We show that infecting trypanosome has diverged from classical strains lacks defense mechanism serum. By sequencing gene of subsequent vitro mutagenesis experiments, demonstrate homozygous missense substitution (N264K) membrane-addressing domain variant knocks down trypanolytic activity, allowing avoid ApoL1-mediated immunity. IMPORTANCE Most Only lysis specific proteins. here hypothesize interacts with endolysosomal membranes trypanosomes. The N264K lytic activity lacking if accompanied substitutions SRA-interacting domain. Our data suggest populations frequencies may be at increased risk contracting trypanosomiasis.