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Dive into the research topics where Luc Vanhamme is active.

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Featured researches published by Luc Vanhamme.


Nature | 2003

Apolipoprotein L-I is the trypanosome lytic factor of human serum.

Luc Vanhamme; Françoise Paturiaux-Hanocq; Philippe Poelvoorde; Derek P. Nolan; Laurence Lins; Jan Van Den Abbeele; Annette Pays; Patricia Tebabi; Huang Van Xong; Alain Jacquet; Nicole Moguilevsky; Marc Dieu; John P. Kane; Patrick De Baetselier; Robert Brasseur; Etienne Pays

Human sleeping sickness in east Africa is caused by the parasite Trypanosoma brucei rhodesiense. The basis of this pathology is the resistance of these parasites to lysis by normal human serum (NHS). Resistance to NHS is conferred by a gene that encodes a truncated form of the variant surface glycoprotein termed serum resistance associated protein (SRA). We show that SRA is a lysosomal protein, and that the amino-terminal α-helix of SRA is responsible for resistance to NHS. This domain interacts strongly with a carboxy-terminal α-helix of the human-specific serum protein apolipoprotein L-I (apoL-I). Depleting NHS of apoL-I, by incubation with SRA or anti-apoL-I, led to the complete loss of trypanolytic activity. Addition of native or recombinant apoL-I either to apoL-I-depleted NHS or to fetal calf serum induced lysis of NHS-sensitive, but not NHS-resistant, trypanosomes. Confocal microscopy demonstrated that apoL-I is taken up through the endocytic pathway into the lysosome. We propose that apoL-I is the trypanosome lytic factor of NHS, and that SRA confers resistance to lysis by interaction with apoL-I in the lysosome.


Cell | 1998

A VSG Expression Site–Associated Gene Confers Resistance to Human Serum in Trypanosoma rhodesiense

Hoang Van Xong; Luc Vanhamme; Mustapha Chamekh; Chibeka Evelyn Chimfwembe; Jan Van Den Abbeele; Annette Pays; Nestor Van Meirvenne; Raymond Hamers; Patrick De Baetselier; Etienne Pays

Infectivity of Trypanosoma brucei rhodesiense to humans is due to its resistance to a lytic factor present in human serum. In the ETat 1 strain this character was associated with antigenic variation, since expression of the ETat 1.10 variant surface glycoprotein was required to generate resistant (R) clones. In addition, in this strain transcription of a gene termed SRA was detected in R clones only. We show that the ETat 1.10 expression site is the one selectively transcribed in R variants. This expression site contains SRA as an expression site-associated gene (ESAG) and is characterized by the deletion of several ESAGs. Transfection of SRA into T.b. brucei was sufficient to confer resistance to human serum, identifying this gene as one of those responsible for T.b. rhodesiense adaptation to humans.


Nature Reviews Microbiology | 2006

The trypanolytic factor of human serum.

Etienne Pays; Benoit Vanhollebeke; Luc Vanhamme; Françoise Paturiaux-Hanocq; Derek P. Nolan; David Perez-Morga

African trypanosomes (the prototype of which is Trypanosoma brucei brucei) are protozoan parasites that infect a wide range of mammals. Human blood, unlike the blood of other mammals, has efficient trypanolytic activity, and this needs to be counteracted by these parasites. Resistance to this activity has arisen in two subspecies of Trypanosoma brucei — Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense — allowing these parasites to infect humans, and this results in sleeping sickness in East Africa and West Africa, respectively. Study of the mechanism by which T. b. rhodesiense escapes lysis by human serum led to the identification of an ionic-pore-forming apolipoprotein — known as apolipoprotein L1 — that is associated with high-density-lipoprotein particles in human blood. In this Opinion article, we argue that apolipoprotein L1 is the factor that is responsible for the trypanolytic activity of human serum.


Molecular Microbiology | 2000

Differential RNA elongation controls the variant surface glycoprotein gene expression sites of Trypanosoma brucei.

Luc Vanhamme; Philippe Poelvoorde; Annette Pays; Patricia Tebabi; Hoang Van Xong; Etienne Pays

The protozoan parasite Trypanosoma brucei develops antigenic variation to escape the immune response of its host. To this end, the trypanosome genome contains multiple telomeric expression sites competent for transcription of variant surface glycoprotein genes, but as a rule only a single antigen is expressed at any time. We used reverse transcription‐PCR (RT‐PCR) to analyse transcription of different segments of the expression sites in different variant clones of two independent strains of T. brucei. The results indicated that RNA polymerase is installed and active at the beginning of many, if not all, expression sites simultaneously, but that a progressive arrest of RNA elongation occurs in all but one site. This defect is linked to inefficient RNA processing and RNA release from the nucleus. Therefore, functional transcription in the active site appears to depend on the selective recruitment of a RNA elongation/processing machinery.


Trends in Parasitology | 2001

An update on antigenic variation in African trypanosomes

Luc Vanhamme; Etienne Pays; Richard McCulloch; J. David Barry

African trypanosomes can spend a long time in the blood of their mammalian host, where they are exposed to the immune system and are thought to take advantage of it to modulate their own numbers. Their major immunogenic protein is the variant surface glycoprotein (VSG), the gene for which must be in one of the 20--40 specialized telomeric expression sites in order to be transcribed. Trypanosomes escape antibody-mediated destruction through periodic changes of the expressed VSG gene from a repertoire of approximately 1000. How do trypanosomes exclusively express only one VSG and how do they switch between them?


PLOS ONE | 2008

Ir-LBP, an Ixodes ricinus Tick Salivary LTB4-Binding Lipocalin, Interferes with Host Neutrophil Function

Jérôme Beaufays; Benoı̂t Adam; Catherine Menten-Dedoyart; Laurence Fievez; Amélie Grosjean; Yves Decrem; Pierre-Paul Prévot; Sébastien Santini; Robert Brasseur; Michel Brossard; Michel Vanhaeverbeek; Fabrice Bureau; Ernst Heinen; Laurence Lins; Luc Vanhamme; Edmond Godfroid

Background During their blood meal, ticks secrete a wide variety of proteins that can interfere with their hosts defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. Methodology/Principal Findings We previously identified 14 new lipocalin genes in the tick Ixodes ricinus. One of them codes for a protein that specifically binds leukotriene B4 with a very high affinity (Kd: ±1 nM), similar to that of the neutrophil transmembrane receptor BLT1. By in silico approaches, we modeled the 3D structure of the protein and the binding of LTB4 into the ligand pocket. This protein, called Ir-LBP, inhibits neutrophil chemotaxis in vitro and delays LTB4-induced apoptosis. Ir-LBP also inhibits the host inflammatory response in vivo by decreasing the number and activation of neutrophils located at the tick bite site. Thus, Ir-LBP participates in the ticks ability to interfere with proper neutrophil function in inflammation. Conclusions/Significance These elements suggest that Ir-LBP is a “scavenger” of LTB4, which, in combination with other factors, such as histamine-binding proteins or proteins inhibiting the classical or alternative complement pathways, permits the tick to properly manage its blood meal. Moreover, with regard to its properties, Ir-LBP could possibly be used as a therapeutic tool for illnesses associated with an increased LTB4 production.


Journal of Biological Chemistry | 1998

Trypanosoma brucei TBRGG1, a mitochondrial oligo(U)-binding protein that co-localizes with an in vitro RNA editing activity.

Luc Vanhamme; David Perez-Morga; Christian Marchal; Dave Speijer; Laurence Lambert; Maurice Geuskens; Sylvie Alexandre; Naima Ismaili; Ulrich Göringer; Rob Benne; Etienne Pays

We report the characterization of aTrypanosoma brucei 75-kDa protein of the RGG (Arg-Gly-Gly) type, termed TBRGG1. Dicistronic and monocistronic transcripts of theTBRGG1 gene were produced by both alternative splicing and polyadenylation. TBRGG1 was found in two or three forms that differ in their electrophoretic mobility on SDS-polyacrylamide gel electrophoresis gels, one of which was more abundant in the procyclic form of the parasite. TBRGG1 was localized to the mitochondrion and appeared to be more abundant in bloodstream intermediate and stumpy forms in which the mitochondrion reactivates and during the procyclic stage, which possesses a fully functional mitochondrion. This protein was characterized to display oligo(U) binding characteristics and was found to co-localize with an in vitro RNA editing activity in a sedimentation analysis. TBRGG1 most likely corresponds to the 83-kDa oligo(U)-binding protein previously identified by UV cross-linking of guide RNA to mitochondrial lysates (Leegwater, P., Speijer, D., and Benne, R. (1995) Eur. J. Biochem.227, 780–786).


PLOS ONE | 2008

Variability and Action Mechanism of a Family of Anticomplement Proteins in Ixodes ricinus

Bernard Couvreur; Jérôme Beaufays; Cédric Charon; Kathia Lahaye; Francois Gensale; Valérie Denis; Benoit Charloteaux; Yves Decrem; Pierre -Paul Prevot; Michel Brossard; Luc Vanhamme; Edmond Godfroid

Background Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. Methodology/Principal Findings We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in Ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical or functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Conclusions/Significance Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway. Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods.


Molecular and Biochemical Parasitology | 1998

Genetic nomenclature for Trypanosoma and Leishmania

Christine Clayton; Mark D. Adams; Renata Almeida; Théo Baltz; Michael P. Barrett; Patrick Bastien; Sabina I. Belli; Stephen M. Beverley; Nicolas Biteau; Jenefer M. Blackwell; Christine Blaineau; Michael Boshart; Frédéric Bringaud; George A.M. Cross; Angela K. Cruz; Wim Degrave; John E. Donelson; Najib M. El-Sayed; Gioliang Fu; Klaus Ersfeld; Wendy Gibson; Keith Gull; Alasdair Ivens; John M. Kelly; Daniel Lawson; John Lebowitz; Phelix A.O. Majiwa; Keith R. Matthews; Sara E. Melville; Gilles Merlin

Christine Clayton *, Mark Adams , Renata Almeida , Theo Baltz , Mike Barrett , Patrick Bastien , Sabina Belli , Stephen Beverley , Nicolas Biteau , Jenefer Blackwell , Christine Blaineau , Michael Boshart , Frederic Bringaud , George Cross , Angela Cruz , Wim Degrave , John Donelson , Najib El-Sayed , Gioliang Fu , Klaus Ersfeld , Wendy Gibson , Keith Gull , Alasdair Ivens , John Kelly , Daniel Lawson , John Lebowitz , Phelix Majiwa , Keith Matthews , Sara Melville , Gilles Merlin , Paul Michels , Peter Myler , Alan Norrish , Fred Opperdoes , Barbara Papadopoulou , Marilyn Parsons , Thomas Seebeck , Deborah Smith , Kenneth Stuart , Michael Turner , Elisabetta Ullu , Luc Vanhamme aa


The EMBO Journal | 1995

The 3'-terminal region of the mRNAs for VSG and procyclin can confer stage specificity to gene expression in Trypanosoma brucei.

M Berberof; Luc Vanhamme; Patricia Tebabi; Annette Pays; D Jefferies; Susan C. Welburn; Etienne Pays

The variant surface glycoprotein (VSG) and procyclin are the respective major surface antigens of the bloodstream and the procyclic forms of Trypanosoma brucei. These proteins and their mRNAs are both the most abundant and absolutely characteristic of their respective life cycle stages. We show that the 3′‐terminal region of these mRNAs regulates expression of a reporter gene in an inverse manner, depending on the developmental form of the parasite. In the case of VSG mRNA, the 97 nt sequence upstream from the polyadenylation site is responsible for these effects. The regulation occurs through a variation of mRNA abundance which is not due to a change in primary transcription. In the bloodstream form this effect is manifested by an increase in RNA stability, whereas in the procyclic form it seems to be related to a reduction in the efficiency of mRNA maturation. The 3′‐end of VSG mRNA can obviate the 5‐ to 10‐fold stimulation of transcription driven by the procyclin promoter during differentiation from the bloodstream to the procyclic form. The predominance of posttranscriptional over transcriptional controls is probably linked to the organization of the trypanosome genome in polycistronic transcription units.

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Etienne Pays

Université libre de Bruxelles

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Pierre Van Antwerpen

Université libre de Bruxelles

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Cédric Delporte

Université libre de Bruxelles

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Alexandre Rousseau

Université libre de Bruxelles

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Michel Vanhaeverbeek

Université libre de Bruxelles

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Philippe Poelvoorde

Université libre de Bruxelles

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Jean Neve

Université libre de Bruxelles

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Caroline Noyon

Université libre de Bruxelles

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Nicole Moguilevsky

Université libre de Bruxelles

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