References of "Willems, Luc"
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See detailPhysiological and bio-functional properties of gum arabic: a notable interest for certain human diseases
Eloundou Mballa, Pierre; Goffin, Dorothée ULg; Destain, Jacqueline ULg et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (in press)

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See detailModes of Human T Cell Leukemia Virus Type 1 Transmission, Replication and Persistence
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Hamaïdia, Malik ULg et al

in Viruses (2015), 7

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes cancer (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly HTLV-associated myelopathy—tropical spastic ... [more ▼]

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes cancer (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly HTLV-associated myelopathy—tropical spastic paraparesis, HAM/TSP). Since virions are particularly unstable, HTLV-1 transmission primarily occurs by transfer of a cell carrying an integrated provirus. After transcription, the viral genomic RNA undergoes reverse transcription and integration into the chromosomal DNA of a cell from the newly infected host. The virus then replicates by either one of two modes: (i) an infectious cycle by virus budding and infection of new targets and (ii) mitotic division of cells harboring an integrated provirus. HTLV-1 replication initiates a series of mechanisms in the host including antiviral immunity and checkpoint control of cell proliferation. HTLV-1 has elaborated strategies to counteract these defense mechanisms allowing continuous persistence in humans. [less ▲]

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See detailAPOBEC3 Interference during Replication of Viral Genomes
Willems, Luc ULg; Gillet, Nicolas ULg

in Viruses (2015)

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See detailCheckpoints modulation by the human T-lymphotropic virus type 1 (HTLV-1) Tax protein : towards new therapeutic approaches
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Boxus, Mathieu et al

Poster (2015, May 13)

HTLV-1 infects approximately 15 million people worldwide and causes several diseases. This virus is responsible for the adult T-cell leukemia (ATL) and for a chronic neuropathology (TSP/HAM). There is ... [more ▼]

HTLV-1 infects approximately 15 million people worldwide and causes several diseases. This virus is responsible for the adult T-cell leukemia (ATL) and for a chronic neuropathology (TSP/HAM). There is currently no satisfactory treatment for these diseases. Among the proteins encoded by HTLV-1, Tax appears to play an important role in the mechanisms leading to pathogenicity. We are interested in the mechanisms of cell transformation by the Tax viral oncoprotein. In particular, we aim at understanding the interplay between Tax and the DNA damage response (DDR). We show that transient expression of Tax results in DNA damage, cell cycle arrest and activation of the DDR. In fibroblasts, cell cycle arrest occurs at the G1 and G2 phases depending on the p53 background. In contrast, HTLV-1 infected lymphocytes proliferate continuously and appear to be adapted to the checkpoints. This mechanism of checkpoint adaptation thus allows ongoing proliferation despite the presence of genomic lesions. Quantification of the rates of NHEJ and homologous recombination indicates that HTLV-1 infected cells require very efficient DNA repair for survival. Therefore, we propose a novel therapeutic approach based on the principle of synthetic lethality using inhibitors of DNA repair. [less ▲]

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See detailInteraction of HTLV-1 Tax with minichromosome maintenance proteins modulates viral transcription
Barez, Pierre-Yves ULg; Carpentier, Alexandre ULg; Boxus, Mathieu et al

Poster (2015, May 13)

First human retrovirus discovered, HTLV-1 infects approximately twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases that include adult T-cell leukemia (ATL) and a ... [more ▼]

First human retrovirus discovered, HTLV-1 infects approximately twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases that include adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). We are interested in the mechanisms of transformation by the viral Tax oncoprotein. We previously showed that Tax interacts with the minichromosome maintenance MCM2-7 helicase and affects host cell replication (Boxus et al, 2012 Blood 119:151). In this project, we focused on the role of the MCM2-7 complex in transcription. We first show by chromatin immunoprecipitation that the MCM2-7 is recruited onto the 5'-LTR promoter. The 5’-LTR does however not act as a DNA replication origin. In contrast, MCM2-7 activates viral transcription as revealed by luciferase reporter assays. Interaction between Tax and MCM2-7 also affect expression of cellular genes. Together, our data thus demonstrate that the viral promoter is not a replication origin and that interaction between Tax and MCM2-7 is involved in the viral transcription. [less ▲]

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See detailReprogramming of replication origin firing and checkpoint adaptation in adult T-cell leukemia
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Boxus, Mathieu et al

Conference (2015, February 11)

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the ... [more ▼]

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). A key parameter of HTLV-1 pathogenesis is faster replication of provirus-carrying lymphocytes allowing clonal expansion of infected cell populations. The virally-encoded Tax oncoprotein plays an essential role in this process by interacting with DNA replication origins and accelerating S phase progression. By reprogramming the timing of origin firing, Tax also creates a replicative stress leading to DNA double strand breaks. This mechanism further triggers the DNA damage response (DDR) that induces cell cycle arrest and initiates either apoptosis or senescence. However, HTLV-1 infected cells have developed strategies to interfere with the DDR and are adapted to checkpoint control. These cells are thus able to proliferate despite occurrence of DNA damage. Based on these observations, we now propose a novel therapeutic approach based on the principle of synthetic lethality. [less ▲]

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See detailCheckpoints modulation by the human T-lymphotropic virus type 1 (HTLV-1) Tax protein : towards new therapeutic approaches
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Boxus, Mathieu et al

Poster (2015, February 11)

HTLV-1 infects approximately 20 million people worldwide and causes several diseases. This virus is responsible for the adult T-cell leukemia (ATL) and for a chronic neuropathology (TSP/HAM). There is ... [more ▼]

HTLV-1 infects approximately 20 million people worldwide and causes several diseases. This virus is responsible for the adult T-cell leukemia (ATL) and for a chronic neuropathology (TSP/HAM). There is currently no satisfactory treatment for these diseases. Among the proteins encoded by HTLV-1, Tax appears to play an important role in the mechanisms leading to pathogenicity. We are interested in the mechanisms of cell transformation by HTLV-1 and more particularly in the interplay between the viral Tax oncoprotein and the DNA damage response (DDR). We demonstrate that transient expression of Tax results in DNA damage, cell cycle arrest and activation of the ATM-Chk2-p53 axis of the DDR. In fibroblasts, cell cycle arrest occurs at the G1 and G2 phases depending on the p53 background. Despite Tax expression hampers cell cycle progression, neither pro-apoptotic nor pro-senescent effects are observed. In contrast, HTLV-1 infected lymphocytes proliferate continuously and appear to be adapted to the checkpoints. This mechanism allows infected lymphocytes to proliferate despite the presence of genomic lesions. Those cells might thus rely on effective DNA repair mechanisms. Indeed, we show that Tax expressing cells activate the error free repair mechanism homologous recombination (HR). Inhibition of ATM, involved in DDR and DNA repair by HR, impedes Tax-mediated cellular transformation. Depending on these observations, we propose a novel therapeutic approach based on the principle of synthetic lethality. [less ▲]

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See detailRisk of emergence of a hyperpathogenic bovine leukemia virus by mutation of a single envelope N-linked glycosylation site
De Brogniez, Alix ULg; Bouzar, Amel-Baya; Jacques, Jean-Rock ULg et al

Poster (2015, February 11)

- Introduction : Pathogens have co-evolved with their host to ensure efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is ... [more ▼]

- Introduction : Pathogens have co-evolved with their host to ensure efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by the bovine leukemia virus (BLV) system in which lymphoproliferative disorders develop in ruminants after latency periods of several years. Infection of sheep and cattle with BLV is a model system for the related human T-lymphotropic virus type 1 (HTLV-1) responsible for Adult T-cell Leukemia (ATL). - Aims : The goal of this work is to investigate the role of N-glycans of the viral envelope protein during viral replication and pathogenesis. - Methods and results : Using glycosylation inhibitors and lectins, we showed that N-glycosylation is involved in viral infection (i.e. cell-to-cell fusion). Using reverse genetics of an infectious molecular provirus, we next demonstrated that a particular N-linked envelope glycosylation site (N230) limits viral replication and pathogenicity in vitro and in vivo. We have thus generated a viral mutant that is more pathogenic than the wild type strain. - Conclusions : To our knowledge, this is the first time that a hyperpathogenic BLV has been identified. This unexpected observation has important consequences in terms of disease control and managing. Indeed, during evolution, pathogens and their hosts should achieve an equilibrium allowing the coexistence of the two species. Occurrence of this particular mutation may thus represent a potential threat associated with emergence of hyperpathogenic BLV strains and possibly of new variants of the related HTLV-1. [less ▲]

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See detailReprogramming of replication origin firing and checkpoint adaptation in adult T-cell leukemia
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Boxus, Mathieu et al

Conference (2015, February 03)

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the ... [more ▼]

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). A key parameter of HTLV-1 pathogenesis is faster replication of provirus-carrying lymphocytes allowing clonal expansion of infected cell populations. The virally-encoded Tax oncoprotein plays an essential role in this process by interacting with DNA replication origins and accelerating S phase progression. By reprogramming the timing of origin firing, Tax also creates a replicative stress leading to DNA double strand breaks. This mechanism further triggers the DNA damage response (DDR) that induces cell cycle arrest and initiates either apoptosis or senescence. However, HTLV-1 infected cells have developed strategies to interfere with the DDR and are adapted to checkpoint control. These cells are thus able to proliferate despite occurrence of DNA damage. Based on these observations, we now propose a novel therapeutic approach based on the principle of synthetic lethality. [less ▲]

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See detailMutation of a Single Envelope N-linked Glycosylation Site Enhances the Pathogenicity of Bovine Leukemia Virus
De Brogniez, Alix ULg; Bouzar, Amel-Baya; Jacques, Jean-Rock ULg et al

in Journal of Virology (2015), 89(17),

Viruses have co-evolved with their host to ensure efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by the ... [more ▼]

Viruses have co-evolved with their host to ensure efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by the bovine leukemia virus (BLV) system in which lymphoproliferative disorders develop in ruminants after latency periods of several years. In principle, the equilibrium reached between the virus and its host could be disrupted by emergence of more pathogenic strains. Intriguingly but fortunately, such a hyperpathogenic BLV strain was never observed in the field nor designed in vitro. In this study, we aimed at understanding the role of envelope N-linked glycosylation with the hypothesis that this posttranslational modification could either favor BLV infection by allowing viral entry or allow immune escape by using glycans as a shield. Using reverse genetics of an infectious molecular provirus, we have identified a N-linked envelope glycosylation site (N230) that limits viral replication and pathogenicity. Indeed, mutation N230E unexpectedly leads to enhanced fusogenicity and protein stability. Occurrence of this mutation may thus represent a potential threat associated with emergence of hyperpathogenic BLV strains and possibly of new variants of the related primate T-lymphotropic viruses. [less ▲]

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See detailPlant polysaccharides initiate underground crosstalk with bacilli by inducing synthesis of the immunogenic lipopeptide surfactin
Debois, Delphine ULg; Fernandez, O.; Franzil, Laurent ULg et al

in Environmental Microbiology Reports (2015), 7(3), 570-582

Some plant-associated bacteria such as Bacillus sp. can protect their host from pathogen ingress and this biocontrol activity correlates with their potential to form multiple antibiotics upon in vitro ... [more ▼]

Some plant-associated bacteria such as Bacillus sp. can protect their host from pathogen ingress and this biocontrol activity correlates with their potential to form multiple antibiotics upon in vitro growth. However, our knowledge on antibiotic production by soil bacilli evolving on roots in natural conditions is still limited. In this work, antibiome imaging first revealed that the lipopeptide surfactin is the main bacterial ingredient produced in planta within the first hours of interaction with root tissues. We further demonstrated that surfactin synthesis is specifically stimulated upon perception of plant cell wall polymers such as xylan or arabinogalactan, leading to fast accumulation of micromolar amounts in the root environment. At such concentrations, the lipopeptide may not only favour the ecological fitness of the producing strain in term of root colonization, but also triggers systemic resistance in the host plant. This surfactin-induced immunity primes the plant to better resist further pathogen ingress, and involves only limited expression of defence-related molecular events and does not provoke seedling growth inhibition. By contrast with the strong response mounted upon perception of pathogens, this strongly attenuated defensive reaction induced by surfactin in plant tissues should help Bacillus to be tolerated as saprophytic partner by its host. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd. [less ▲]

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See detailStructural Characterization, Technological Functionality and Physiological Aspects of Fungal β-D-Glucans : A Review
Borchani, Chema; Fonteyn, Fabienne; Jamin, Guilhem et al

in Critical Reviews in Food Science & Nutrition (2015)

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See detailRisk of emergence of a hyperpathogenic bovine leukemia virus by mutation of a single envelope N-linked glycosylation site
De Brogniez, Alix ULg; Bouzar, Amel-Baya; Jacques, Jean-Rock ULg et al

Scientific conference (2014, December 08)

Pathogens have co-evolved with their host to allow efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by ... [more ▼]

Pathogens have co-evolved with their host to allow efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by the bovine leukemia virus (BLV) model that induces lymphoproliferative disorders in ruminants only after extended latency periods of several years. In principle, the equilibrium reached between the virus and its host could be disrupted by emergence of more pathogenic strains. Intriguingly, this type of hyperpathogenic BLV strain could never been isolated in vivo nor designed in vitro. Using reverse genetics of an infectious molecular provirus, we have now identified a N-linked envelope glycosylation site that limits viral replication and pathogenicity. Onset of this particular mutation may thus represent a potential threat associated with emergence of hyperpathogenic BLV strains and possibly of new variants of the related primate T-lymphotropic viruses. [less ▲]

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See detailEpigenetic regulation of macrophage polarisation
Hamaïdia, Malik ULg; Cosse, Jean-Philippe ULg; Willems, Luc ULg

Scientific conference (2014, October 10)

Présentation des résultats devant les promoteurs membres de l'axe 4 Agricuture is life (plateforme Gembloux AgroBiotech)

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See detailA Single Envelope N-linked Glycosylation Site Defines Hyperpathogenicity of Bovine Leukemia Virus
De Brogniez, Alix ULg; Bouzar, Amel-Baya; Jacques, Jean-Rock ULg et al

Conference (2014, June 05)

Pathogens have co-evolved with their host to allow efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by ... [more ▼]

Pathogens have co-evolved with their host to allow efficient replication and transmission without inducing excessive pathogenicity that would indirectly impair their persistence. This is exemplified by the bovine leukemia virus (BLV) model that induces lymphoproliferative disorders in ruminants only after extended latency periods of several years. In principle, the equilibrium reached between the virus and its host could be disrupted by emergence of more pathogenic strains. Intriguingly, this type of hyperpathogenic BLV strain could never been isolated in vivo nor designed in vitro. Using reverse genetics of an infectious molecular provirus, we have now identified a N-linked envelope glycosylation site that limits viral replication and pathogenicity. Onset of this particular mutation may thus represent a potential threat associated with emergence of hyperpathogenic BLV strains and possibly of new variants of the related primate T-lymphotropic viruses. [less ▲]

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See detailEpigenetic regulation of macrophage polarisation
Hamaïdia, Malik ULg; Cosse, Jean-Philippe ULg; Willems, Luc ULg

Conference (2014, May 19)

There are two main macrophage subsets based on their cytokine pattern and phenotype: classical (or M1) and alternative (or M2). M1 macrophages promote anti-tumor immunity by supporting polarization of CD4 ... [more ▼]

There are two main macrophage subsets based on their cytokine pattern and phenotype: classical (or M1) and alternative (or M2). M1 macrophages promote anti-tumor immunity by supporting polarization of CD4 T-lymphocytes into anti-tumor Th1 and Th17. On the other hand, tumor associated macrophages (TAMs) that are close to M2 promote survival and proliferation of tumor cells. Evidence indicates that macrophage polarization is mediated by a transcriptional program that is influenced by epigenetic modifications. We investigated the effect of different epigenetic inhibitors on polarization of human macrophages. After isolation of human peripheral blood mononuclear cells, macrophages were polarized into M1 (using LPS+IFN-gamma) or M2 (with IL4) in presence or absence of inhibitors. Flow cytometry analyzes showed that epigenetic modulation affects CD206 expression on M2 macrophages, dextran-FITC phagocytosis and proliferation of allogeneic T-lymphocytes. Epigenetic inhibitors thus affect polarisation into M2 and may be useful to improve immunotherapy of cancer. [less ▲]

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See detailReprogramming of replication origin firing and checkpoint adaptation in adult T cell leukemia
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Boxus, Mathieu et al

Conference (2014, May 02)

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the ... [more ▼]

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about twenty million individuals worldwide. HTLV-1 is the causative agent of different diseases among which the most common are the adult T-cell leukemia (ATL) and a neurodegenerative disorder called HAM/TSP (Human associated myelopathy/ Tropical spastic paraparesis). A key parameter of HTLV-1 pathogenesis is faster replication of provirus-carrying lymphocytes allowing clonal expansion of infected cell populations. The virally-encoded Tax oncoprotein plays an essential role in this process by interacting with DNA replication origins and accelerating S phase progression. By reprogramming the timing of origin firing, Tax also creates a replicative stress leading to DNA double strand breaks. This mechanism further triggers the DNA damage response (DDR) that induces cell cycle arrest and initiates either apoptosis or senescence. However, HTLV-1 infected cells have developed strategies to interfere with the DDR and are adapted to checkpoint control. These cells are thus able to proliferate despite occurrence of DNA damage. Based on these observations, we now propose a novel therapeutic approach based on the principle of synthetic lethality. [less ▲]

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See detailEpigenetic regulation of macrophage polarisation
Hamaïdia, Malik ULg; Cosse, Jean-Philippe ULg; Willems, Luc ULg

Poster (2014, April 29)

There are two main macrophage subsets based on their cytokine pattern and phenotype: classical (or M1) and alternative (or M2). M1 macrophages promote anti-tumor immunity by supporting polarization of CD4 ... [more ▼]

There are two main macrophage subsets based on their cytokine pattern and phenotype: classical (or M1) and alternative (or M2). M1 macrophages promote anti-tumor immunity by supporting polarization of CD4 T-lymphocytes into anti-tumor Th1 and Th17. On the other hand, tumor associated macrophages (TAMs) that are close to M2 promote survival and proliferation of tumor cells. Evidence indicates that macrophage polarization is mediated by a transcriptional program that is influenced by epigenetic modifications. We investigated the effect of different epigenetic inhibitors on polarization of human macrophages. After isolation of human peripheral blood mononuclear cells, macrophages were polarized into M1 (using LPS+IFN-gamma) or M2 (with IL4) in presence or absence of inhibitors. Flow cytometry analyzes showed that epigenetic modulation affects CD206 expression on M2 macrophages, dextran-FITC phagocytosis and proliferation of allogeneic T-lymphocytes. Epigenetic inhibitors thus affect polarisation into M2 and may be useful to improve immunotherapy of cancer. [less ▲]

Detailed reference viewed: 30 (6 ULg)