The table has four columns and six rows. The columns are labeled Human defense, Parasite, Disease, and Location. The table details the interactions between human defenses and various trypanosome parasites, the diseases they cause, and their geographical locations. Row 1: A P O L 1 kills Trypanosoma brucei brucei, resulting in no disease, and occurs in Sub-Saharan Africa. Row 2: A P O L 1 defense is blocked by the parasite factor S R A, allowing Trypanosoma brucei rhodesiense infection that causes acute sleeping sickness in Eastern Africa. Row 3: A P O L 1 activity is resisted by the parasite factor T g s G P, enabling Trypanosoma brucei gambiense infection that causes chronic sleeping sickness in Western Africa. Row 4: A P O L 1 knockout (rare) allows infection by Trypanosoma evansi, leading to atypical human infection reported in India. Row 5: A P O L 1 G 1 slash G 2 variants (frequent) provide resistance to Trypanosoma brucei rhodesiense but are associated with kidney disease in Western Africa. Row 6: A P O L 1 G 1/G 2 with the N 264 K variant (rare) also confers resistance to Trypanosoma brucei rhodesiense with no specified disease, occurring in Western Africa.
Molecular ‘arms race’ between African trypanosomes and humans. Human ancestors produced a secreted version of APOL1 to kill the bloodstream parasite T. brucei brucei (9). Two T. brucei brucei clones, known as T. brucei rhodesiense and T. brucei gambiense, can neutralize APOL1 through either direct interaction of the T. brucei rhodesiense-specific SRA with APOL1, or T. brucei gambiense-specific TgsGP interference with APOL1 activity (9, 91). A rare Indian case of APOL1 KO due to frameshift mutations in both APOL1 alleles resulted in atypical infection by T. brucei brucei-like T. evansi parasites (92). The APOL1 C-terminal variants G1 and G2, widespread in Western Africa, can restore human resistance to T. brucei rhodesiense through interference with SRA–APOL1 interaction (7). However, the G1 or G2 mutations also confer high probability of humans developing chronic kidney disease (7). APOL1 variants with the N264K mutation can still efficiently kill T. brucei rhodesiense but no longer exhibit kidney podocyte cytotoxicity (65, 66, 93) ( →: APOL1 trypanolytic activity; ✖: trypanosome lysis; ---: no disease).