Apolipoprotein L1 variant associated with increased susceptibility to trypanosome infection
| Autor: | Kris Laukens, Bart Cuypers, Thomas Azurago, Prince Homiah, Michael D. Lewis, Laurence Lecordier, Conor J. Meehan, José R. Franco, Etienne Pays, Achim Schnaufer, Ebenezer Kofi Mensah, Frederik Van den Broeck, Caroline E. Dewar, Stijn Deborggraeve, Sardick Kyei-Faried, Oliver Balmer, Sally-Ann Ohene, Jean-Claude Dujardin, Hideo Imamura, Boateng Duah, Philippe Büscher, Francis Anleah |
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| Přispěvatelé: | Faculty of Law and Criminology, Clinical sciences, Medical Genetics, Department of Bio-engineering Sciences, Vriendenkring VUB |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Trypanosoma brucei rhodesiense
0301 basic medicine Apolipoprotein L1 Trypanosoma brucei gambiense Mutation Missense Protozoan Proteins Mutagenesis (molecular biology technique) Polymorphism Single Nucleotide Microbiology 03 medical and health sciences Immunity Virology medicine Humans African trypanosomiasis Biology chemistry.chemical_classification Genetics biology Genetic Variation medicine.disease biology.organism_classification Immunity Innate QR1-502 3. Good health Ingénierie biomédicale Apolipoproteins Trypanosomiasis African 030104 developmental biology chemistry biology.protein Trypanosoma Human medicine Disease Susceptibility Lipoproteins HDL Glycoprotein Microbiologie et protistologie [bacteriol.virolog.mycolog.] Trypanosomiasis Research Article |
| Zdroj: | MBio, 7 (2 Cuypers, B, Lecordier, L, Meehan, C J, Van den Broeck, F, Imamura, H, Büscher, P, Dujardin, J-C, Laukens, K, Schnaufer, A, Dewar, C, Lewis, M, Balmer, O, Azurago, T, Kyei-Faried, S, Ohene, S-A, Duah, B, Homiah, P, Mensah, E K, Anleah, F, Franco, J R, Pays, E & Deborggraeve, S 2016, ' Apolipoprotein L1 Variant Associated with Increased Susceptibility to Trypanosome Infection ', mBio, vol. 7, no. 2, e02198-15 . https://doi.org/10.1128/mBio.02198-15 mBio, Vol 7, Iss 2, p e02198-15 (2016) mBio, Vol 7, Iss 2 (2016) mBio |
| ISSN: | 2150-7511 |
| DOI: | 10.1128/mBio.02198-15 |
| Popis: | African trypanosomes, except Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, which cause human African trypanosomiasis, are lysed by the human serum protein apolipoprotein L1 (ApoL1). These two subspecies can resist human ApoL1 because they express the serum resistance proteins T. b. gambiense glycoprotein (TgsGP) and serum resistance-associated protein (SRA), respectively. Whereas in T. b. rhodesiense, SRA is necessary and sufficient to inhibit ApoL1, in T. b. gambiense, TgsGP cannot protect against high ApoL1 uptake, so different additional mechanisms contribute to limit this uptake. Here we report a complex interplay between trypanosomes and an ApoL1 variant, revealing important insights into innate human immunity against these parasites. Using whole-genome sequencing, we characterized an atypical T. b. gambiense infection in a patient in Ghana. We show that the infecting trypanosome has diverged from the classical T. b. gambiense strains and lacks the TgsGP defense mechanism against human serum. By sequencing the ApoL1 gene of the patient and subsequent in vitro mutagenesis experiments, we demonstrate that a homozygous missense substitution (N264K) in the membrane-addressing domain of this ApoL1 variant knocks down the trypanolytic activity, allowing the trypanosome to avoid ApoL1-mediated immunity. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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