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 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 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 ▲]

Detailed reference viewed: 38 (6 ULg)
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 ▲]

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See detailRates of CTL Killing in Persistent Viral Infection In Vivo
Elemans, Marjet; Florins, Arnaud; Willems, Luc ULg et al

in PLoS Computational Biology (2014), 4

The CD8+ cytotoxic T lymphocyte (CTL) response is an important defence against viral invasion. Although CTL-mediated cytotoxicity has been widely studied for many years, the rate at which virus-infected ... [more ▼]

The CD8+ cytotoxic T lymphocyte (CTL) response is an important defence against viral invasion. Although CTL-mediated cytotoxicity has been widely studied for many years, the rate at which virus-infected cells are killed in vivo by the CTL response is poorly understood. To date the rate of CTL killing in vivo has been estimated for three virus infections but the estimates differ considerably, and killing of HIV-1-infected cells was unexpectedly low. This raises questions about the typical anti-viral capability of CTL and whether CTL killing is abnormally low in HIV-1. We estimated the rate of killing of infected cells by CD8+ T cells in two distinct persistent virus infections: sheep infected with Bovine Leukemia Virus (BLV) and humans infected with Human T Lymphotropic Virus type 1 (HTLV-1) which together with existing data allows us to study a total of five viruses in parallel. Although both BLV and HTLV-1 infection are characterised by large expansions of chronically activated CTL with immediate effector function ex vivo and no evidence of overt immune suppression, our estimates are at the lower end of the reported range. This enables us to put current estimates into perspective and shows that CTL killing of HIV-infected cells may not be atypically low. The estimates at the higher end of the range are obtained in more manipulated systems and may thus represent the potential rather than the realised CTL efficiency. [less ▲]

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See detailMassive Depletion of Bovine Leukemia Virus Proviral Clones Located in Genomic Transcriptionally Active Sites During Primary Infection
Gillet, Nicolas ULg; geronimo, gutierrez; rodriguez, sabrina et al

Poster (2014, April)

Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) induce a persistent infection generally asymptomatic but can also lead to leukemia or lymphoma. These ... [more ▼]

Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) induce a persistent infection generally asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate by infecting new lymphocytes (i.e. the infectious cycle) or via clonal expansion of the infected cells (mitotic cycle). The relative importance of these two cycles in viral replication varies during infection. The majority of infected clones are created early before the onset of an efficient immune response. Later on, the main replication route is mitotic expansion of pre-existing infected clones. Due to the paucity of available samples and for ethical reasons, only scarce data is available on early infection by HTLV-1. Therefore, we addressed this question in a comparative BLV model. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the BLV-infected cells population (i.e. the number of distinct clones and abundance of each clone). We found that BLV propagation shifts from cell neoinfection to clonal proliferation in about 2 months from inoculation. Initially, BLV proviral integration significantly favors transcribed regions of the genome. Negative selection then eliminates 97% of the clones detected at seroconversion and disfavors BLV-infected cells carrying a provirus located close to a promoter or a gene. Nevertheless, among the surviving proviruses, clone abundance positively correlates with proximity of the provirus to a transcribed region. Two opposite forces thus operate during primary infection and dictate the fate of long term clonal composition: (1) initial integration inside genes or promoters and (2) host negative selection disfavoring proviruses located next to transcribed regions. The result of this initial response will contribute to the proviral load set point value as clonal abundance will benefit from carrying a provirus in transcribed regions. [less ▲]

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See detailInteractions between new phenolic glycolipids and model membrane
Sainvitu, Pauline ULg; Nasir, Mehmet Nail ULg; Crowet, Jean-Marc ULg et al

Poster (2014, February 07)

Model membrane based on phospholipids (PL) layers are useful to mimic properties of plasma membranes. The interactions between new synthesized phenolic glycolipids (PGL) and biological membrane are ... [more ▼]

Model membrane based on phospholipids (PL) layers are useful to mimic properties of plasma membranes. The interactions between new synthesized phenolic glycolipids (PGL) and biological membrane are crucial to determine their potential as drug candidates and their cytotoxicity . [less ▲]

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See detailEpigenetic modulators mitigate angiogenesis through a complex transcriptomic network
Shiva Shankar, T.V.; Willems, Luc ULg

in Vascular Pharmacology (2014), 60

In this review, we summarize the knowledge pertaining to the role of epigenetics in the regulation of angiogenesis. In particular, we show that lysine acetylation and cytosine methylation are important ... [more ▼]

In this review, we summarize the knowledge pertaining to the role of epigenetics in the regulation of angiogenesis. In particular, we show that lysine acetylation and cytosine methylation are important transcriptional regulators of angiogenic genes in endothelial cells. Lysine acetylation and cytosine methylation inhibitors idiosyncratically tune the transcriptome and affect expression of key modulators of angiogenesis such as VEGF and eNOS. Transcriptomic profiling also reveals a series of novel genes that are concomitantly affected by epigenetic modulators. The reversibility and overall tolerability of currently available epigenetic inhibitors open up the prospect of therapeutic intervention in pathologies where angiogenesis is exacerbated. This type of multitargeted strategy has the major advantage of overcoming the compensatory feedback mechanisms that characterize single anti-angiogenic factors. [less ▲]

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See detailHyper-replicative bovine leukemia virus by mutation of an envelope N-linked glycosylation site
De Brogniez, Alix ULg; Bouzar, Amel-Baya; Jacques, Jean-Rock ULg et al

in Retrovirology (2014), 11(1), 141

Reverse genetics can be used in the bovine leukemia virus (BLV) system to characterize mechanisms of viral persistence and pathogenesis. The question addressed here pertains to the role of glycans bound ... [more ▼]

Reverse genetics can be used in the bovine leukemia virus (BLV) system to characterize mechanisms of viral persistence and pathogenesis. The question addressed here pertains to the role of glycans bound to the BLV envelope glycoprotein (SU). A commonly accepted hypothesis is that addition of carbohydrates to the SU protein potentially creates a structure called « glycan shield » that confers resistance to the virus against the host immune response. On the other hand, glycosylation can also modulate attachment of the virus to the cell membrane. To unravel the role of SU glycosylation, three complementary strategies were developed: pharmacological inhibition of different glycosylation pathways, interference with glycan attachment and site-directed mutagenesis of N-glycosylation sites in an infectious BLV provirus. The different approaches show that glycosylation is required for cell fusion, as expected. Simultaneous mutation of all 8 potential N-glycosylation sites destroys infectivity. Surprisingly, mutation of the asparagine residue at position 230 creates a virus having an increased capacity to form syncytia in vitro. Compared to wild-type BLV, mutant N230 also replicates at accelerated rates in vivo. Collectively, this data thus illustrates an example of a N-glycosylation site that restricts viral replication, contrasting with the hypothesis supported by glycan shield model. [less ▲]

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See detailCheckpoints modulation by the Human T-lymphotropic virus type 1 Tax protein
Carpentier, Alexandre ULg; Barez, Pierre-Yves ULg; Boxus, Mathieu et al

in Retrovirology (2014), 11(S1), 90

HTLV-1 is responsible for two main diseases, Adult T-cell Leukemia/Lymphoma and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis, for which there is currently no satisfactory treatment. Among the ... [more ▼]

HTLV-1 is responsible for two main diseases, Adult T-cell Leukemia/Lymphoma and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis, for which there is currently no satisfactory treatment. 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 Tax and more particularly in the interplay between the viral Tax oncoprotein and the DNA damage response (DDR). We demonstrated 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. Although Tax induces apoptosis and senescence in fibroblasts, HTLV-1 infected lymphocytes proliferate continuously and appear to be adapted to the checkpoint control. This mechanism allows infected lymphocytes to proliferate despite the presence of genomic lesions. With these observations, we propose a novel therapeutic approach based on the principle of synthetic lethality. [less ▲]

Detailed reference viewed: 48 (23 ULg)