References of "Willems, Luc"
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See detailHow Does HTLV-1 Undergo Oncogene-Dependent Replication Despite a Strong Immune Response?
Gazon, Hélène ULiege; Chauhan, Pradeep Singh ULiege; Hamaïdia, Malik ULiege et al

in Frontiers in Microbiology (2018), 8

In 1987, Mitsuaki Yoshida proposed the following model (Yoshida and Seiki, 1987): “... T-cells activated through the endogenous p40x would express viral antigens including the envelope glycoproteins which ... [more ▼]

In 1987, Mitsuaki Yoshida proposed the following model (Yoshida and Seiki, 1987): “... T-cells activated through the endogenous p40x would express viral antigens including the envelope glycoproteins which are exposed on the cell surface. These glycoproteins are targets of host immune surveillance, as is evidenced by the cytotoxic effects of antienvelope antibodies or patient sera. Eventually all cells expressing the viral antigens, that is, all cells driven by the p40x would be rejected by the host. Only those cells that did not express the viral antigens would survive. Later, these antigen-negative infected cells would begin again to express viral antigens, including p40x, thus entering into the second cycle of cell propagation. These cycles would be repeated in so-called healthy virus carriers for 20 or 30 years or longer....” Three decades later, accumulated experimental facts particularly on intermittent viral transcription and regulation by the host immune response appear to prove that Yoshida was right. This Hypothesis and Theory summarizes the evidences that support this paradigm. [less ▲]

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See detailTime to Go Back to the Original Name
Gallo, Robert; Willems, Luc ULiege; Tagaya, Yutaka

in Frontiers in Microbiology (2017), 8

Almost 40 years ago, the first pathogenic human retrovirus was discovered and shown to cause a T-cell leukemia in humans (Poiesz et al., 1980a, 1981). Thus, a new paradigm was established showing that a ... [more ▼]

Almost 40 years ago, the first pathogenic human retrovirus was discovered and shown to cause a T-cell leukemia in humans (Poiesz et al., 1980a, 1981). Thus, a new paradigm was established showing that a virus can directly cause cancer in humans. At that time, the only other suspected case was the connection between the Epstein-Barr Virus (EBV) and Burkitt’s Lymphoma and later nasopharyngeal carcinoma. Naturally, and in keeping with the names used for animal retroviruses associated with leukemia, we (the Gallo group) named this new virus as human T-cell leukemia virus (HTLV), which was formally accepted by the scientific community. As of today, our list of human oncogenic viruses has expanded to include hepatitis B/C virus (HBV, HCV), papillomaviruses (HPV), Herpes virus-8 (HHV-8), and Merkel cell polyomavirus (MCV). In parallel, the group of Delta-retroviruses that HTLV belongs to has expanded to accommodate additionalmembers over the years, now consisting ofHTLV-1_4, and STLV-1_4. In themeantime, the name of the original virus was changed to human T-lymphotropic virus-1, because of the addition of the viral causative agent of AIDS as HTLV-III to the same group (Coffin, 2015). Thus, one of us (RCG) agreed on this name change with several other retrovirologists at a Cold-Spring Harbor meeting in 1983. In retrospect, the name change has made it ambiguous as to which virus should enter this group, and since the AIDS virus was formally named HIV and separated from the HTLV group, making the need for the name of HTLV-1 as human T-“lymphotropic” virus no longer particularly useful or meaningful. Finally, we note here the greater oncogenicity of HTLV-1 compared to other viruses, or even other known carcinogens which is a point in keeping a name that describes their effect (discussed in an accompanying article). Therefore, we propose to restore the original name “leukemia virus.” [less ▲]

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See detailInhibition studies of DNA methyltransferases by maleimide derivatives of RG108 as non-nucleoside inhibitors
Rondelet, Grégoire; Fleury, Laurence; Faux, Céline et al

in Future Medicinal Chemistry (2017), 9(13),

Aim: DNA methyltransferases (DNMTs) are important drug targets for epigenetic therapy of cancer. Nowadays, non-nucleoside DNMT inhibitors are in development to address high toxicity of nucleoside analogs ... [more ▼]

Aim: DNA methyltransferases (DNMTs) are important drug targets for epigenetic therapy of cancer. Nowadays, non-nucleoside DNMT inhibitors are in development to address high toxicity of nucleoside analogs. However, these compounds still have low activity in cancer cells and mode of action of these compounds remains unclear. Materials & methods: In this work, we studied maleimide derivatives of RG108 by biochemical, structural and computational approaches to highlight their inhibition mechanism on DNMTs. Results: Findings demonstrated a correlation between cytotoxicity on mesothelioma cells of these compounds and their inhibitory potency against DNMTs. Noncovalent and covalent docking studies, supported by crystallographic (apo structure of M.HhaI) and differential scanning fluorimetry assays, provided detailed insights into their mode of action and revealed essential residues for the stabilization of such compounds inside DNMTs. [less ▲]

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See detailEGFR tyrosine kinase inhibitors overcome resistance to chemotherapy in malignant pleural mesothelioma.
Staumont, Bernard ULiege; Costa, Christostome; Vandermeers, Fabian et al

Poster (2017, February 01)

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See detailCis-drivers and trans-drivers of bovine leukemia virus oncogenesis
Safari, Roghaiyeh ULiege; Hamaïdia, Malik ULiege; de Brogniez, Alix et al

in Current Opinion in Virology (2017), 26

The bovine leukemia virus (BLV) is a retrovirus inducing an asymptomatic and persistent infection in ruminants and leading in a minority of cases to the accumulation of B-lymphocytes (lymphocytosis ... [more ▼]

The bovine leukemia virus (BLV) is a retrovirus inducing an asymptomatic and persistent infection in ruminants and leading in a minority of cases to the accumulation of B-lymphocytes (lymphocytosis, leukemia or lymphoma). Although the mechanisms of oncogenesis are still largely unknown, there is clear experimental evidence showing that BLV infection drastically modifies the pattern of gene expression of the host cell. This alteration of the transcriptome in infected Blymphocytes results first, from a direct activity of viral proteins (i.e. transactivation of gene promoters, protein–protein interactions), second, from insertional mutagenesis by proviral integration (cis-activation) and third, from gene silencing by microRNAs. Expression of viral proteins stimulates a vigorous immune response that indirectly modifies gene transcription in other cell types (e.g. cytotoxic T-cells, auxiliary T-cells, macrophages). In principle, insertional mutagenesis and microRNA-associated RNA interference can modify the cell fate without inducing an antiviral immunity. Despite a tight control by the immune response, the permanent attempts of the virus to replicate ultimately induce mutations in the infected cell. Accumulation of these genomic lesions and Darwinian selection of tumor clones are predicted to lead to cancer. [less ▲]

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See detailQuantification of Cell Turnover in the Bovine Leukemia Virus Model
De Brogniez, Alix ULiege; Barez, Pierre-Yves; CARPENTIER, Alexandre ULiege et al

in Human T-Lymphotropic Viruses (2017), 1582

In a perspective of a comparative virology approach, characterization of the bovine leukemia virus (BLV) model may be helpful to better understand infection by the related human T-lymphotropic virus type ... [more ▼]

In a perspective of a comparative virology approach, characterization of the bovine leukemia virus (BLV) model may be helpful to better understand infection by the related human T-lymphotropic virus type 1 (HTLV-1). In this paper, we first provide detailed protocols to inoculate cloned BLV proviruses into sheep or cattle. We also describe methods to quantify apoptosis ex vivo and cell turnover in vivo. [less ▲]

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See detailScreening transplant donors for HTLV-1 and -2
Gallo, Robert; Willems, Luc ULiege; Hasegawa, 4 Hideki et al

in Blood (2016), 128(26),

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See detailReducing the global burden of HTLV-1 infection: An agenda for research and action
Willems, Luc ULiege; Hasegawa, Hideki; Accolla, Roberto et al

in Antiviral Research (2016), 137(2017), 41-48

Even though an estimated 10e20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has ... [more ▼]

Even though an estimated 10e20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has been made to reduce its prevalence. In response to this situation, the Global Virus Network launched a taskforce in 2014 to develop new methods of prevention and treatment of HTLV-1 infection and promote basic research. HTLV-1 is the etiological agent of two life-threatening diseases, adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis, for which no effective therapy is currently available. Although the modes of transmission of HTLV-1 resemble those of the more familiar HIV-1, routine diagnostic methods are generally unavailable to support the prevention of new infections. In the present article, the Taskforce proposes a series of actions to expand epidemiological studies; increase research on mechanisms of HTLV-1 persistence, replication and pathogenesis; discover effective treatments; and develop prophylactic and therapeutic vaccines. [less ▲]

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See detailBovine leukemia virus becomes established in dairy herds before the first lactation
Merlini, Ramiro; Gutiérrez, Geronimo; Alvarez, Irene et al

in Archives of Virology (2016), 161

In this work, we studied seven groups of pregnant heifers from a consortium of dairy farms heavily infected with bovine leukemia virus (BLV). ELISA testing showed that the seroprevalence ranges of BLV in ... [more ▼]

In this work, we studied seven groups of pregnant heifers from a consortium of dairy farms heavily infected with bovine leukemia virus (BLV). ELISA testing showed that the seroprevalence ranges of BLV in heifers between 36.1 and 66.5 %. No significant differences in proviral load were found when comparing heifers with adult cattle. Before their first delivery, more than 9.8 % of heifers show a high proviral load. Because BLV infection can occur during the first two years of life, the rationale of any strategy should be to take action as early as possible after birth. [less ▲]

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See detailStructural basis for recognition of histone H3K36me3 nucleosome by human de novo DNA methyltransferases 3A and 3B
Rondelet, Grégoire; Dal Maso, Thomas; Willems, Luc ULiege et al

in Journal of Structural Biology (2016), 194

DNA methylation is an important epigenetic modification involved in chromatin organization and gene expression. The function of DNA methylation depends on cell context and is correlated with histone ... [more ▼]

DNA methylation is an important epigenetic modification involved in chromatin organization and gene expression. The function of DNA methylation depends on cell context and is correlated with histone modification patterns. In particular, trimethylation of Lys36 on histone H3 tail (H3K36me3) is associated with DNA methylation and elongation phase of transcription. PWWP domains of the de novo DNA methyltransferases DNMT3A and DNMT3B read this epigenetic mark to guide DNA methylation. Here we report the first crystal structure of the DNMT3B PWWP domain–H3K36me3 complex. Based on this structure, we propose a model of the DNMT3A PWWP domain–H3K36me3 complex and build a model of DNMT3A (PWWP-ADD-CD) in a nucleosomal context. The trimethylated side chain of Lys36 (H3K36me3) is inserted into an aromatic cage similar to the ‘‘Royal” superfamily domains known to bind methylated histones. A key interaction between trimethylated Lys36 and a conserved water molecule stabilized by Ser270 explains the lack of affinity of mutated DNMT3B (S270P) for the H3K36me3 epigenetic mark in the ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome. The model of the DNMT3A-DNMT3L heterotetramer in complex with a dinucleosome highlights the mechanism for recognition of nucleosome by DNMT3s and explains the periodicity of de novo DNA methylation. [less ▲]

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See detailFrom Valeriana officinalis to cancer therapy: the success of a bio-sourced compound
Hamaïdia, Malik ULiege; Barez, Pierre-Yves ULiege; Carpentier, Alexandre ULiege et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment (2016), 20

Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. In this review, we recapitulate the story ... [more ▼]

Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. In this review, we recapitulate the story of one of these compounds, 2-propylpentanoic acid, derived from the Valeriana officinalis flowering plant and its path to validation as a cancer treatment. [less ▲]

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See detailEGFR tyrosine kinase inhibitors overcome resistance to chemotherapy in malignant pleural mesothelioma.
Staumont, Bernard ULiege; Costa, Christostome; Vandermeers, Fabian et al

in Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016 (2016)

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See detailWhole genome sequencing of 51 breast cancers reveals that tumors are devoid of bovine leukemia virus DNA
Gillet, Nicolas ULiege; Willems, Luc ULiege

in Retrovirology (2016)

Controversy exists regarding the association of bovine leukemia virus (BLV) and breast cancer. PCR-based experimental evidence indicates that BLV DNA is present in breast tissue and that as many as 37% of ... [more ▼]

Controversy exists regarding the association of bovine leukemia virus (BLV) and breast cancer. PCR-based experimental evidence indicates that BLV DNA is present in breast tissue and that as many as 37% of cancer cases may be attributable to viral exposure. Since this association might have major consequences for human health, we evaluated 51 whole genomes of breast cancer samples for the presence of BLV DNA. Among 32 billion sequencing reads retrieved from the NCBI database of genotype and phenotype, none mapped on different strains of the BLV genome. Controls for sequence divergence and proviral loads further validated the approach. This unbiased analysis thus excludes a clonal insertion of BLV in breast tumor cells and strongly argues against an association between BLV and breast cancer. [less ▲]

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See detailGrasshoppers as a food source? A review
Paul, Aman ULiege; Frederich, Michel ULiege; Uyttenbroeck, Roel ULiege et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment (2016), 20(AgricultureIsLife), 337-352

Description of the subject. Current trends suggest an increasing future demand for conventional meats, which indicates a strong need to shift this dependency to other alternative protein sources such as ... [more ▼]

Description of the subject. Current trends suggest an increasing future demand for conventional meats, which indicates a strong need to shift this dependency to other alternative protein sources such as insects. Literature. From a nutritional point of view, of all the insects consumed globally, grasshoppers are particularly important as a human food. Data from the literature regarding the nutrient composition, amino acid profile, fatty acid profile, mineral composition and vitamin content of grasshoppers as reviewed in this paper, suggest that a number of grasshopper species are a good source of nutrients. It also highlights some of the health related aspects that might arise from the consumption of grasshoppers, mostly linked to agricultural practices and the allergic response of sensitive individuals. The paper also summarizes some religious, social and economic factors that are associated with grasshopper consumption. Conclusions. The success of introducing grasshoppers as a novel food in western countries depends on changes in consumer attitudes. It would be interesting to develop food products derived from grasshoppers in a form acceptable to consumers. Furthermore, it is important to explore the food potential of some grasshopper species native to western countries and to develop their rearing methodologies to enhance availability. [less ▲]

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See detailSphingolipids: promising lipid-class molecules with potential applications for industry. A review
Miazek, Krystian ULiege; Lebecque, Simon ULiege; Hamaïdia, Malik ULiege et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment (2016), (20(S1)), 321-336

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See detailImprovement of malignant pleural mesothelioma immunotherapy by epigenetic modulators
Hamaïdia, Malik ULiege; Staumont, Bernard ULiege; DUYSINX, Bernard ULiege et al

in Current Topics in Medicinal Chemistry (2016), 16

In the absence of a satisfactory treatment of malignant pleural mesothelioma (MPM), novel therapeutic strategies are urgently needed. Among these, immunotherapy offers a series of advantages such as tumor ... [more ▼]

In the absence of a satisfactory treatment of malignant pleural mesothelioma (MPM), novel therapeutic strategies are urgently needed. Among these, immunotherapy offers a series of advantages such as tumor specificity and good tolerability. Unfortunately, MPM immunotherapy is frequently limited by incomplete cell differentiation or feedback loop regulatory mechanisms. In this review, we describe different components of the innate immune system and discuss strategies to improve MPM immunotherapy by using epigenetic modulators. [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 (2016), 56(10), 1746-1752

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