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See detailHIV-1 promoter activation following an oxidative stress mediated by singlet oxygen
Legrand, Sylvie ULiege; Hoebeke, Maryse ULiege; Vaira, Dolorès ULiege et al

in Journal of Photochemistry and Photobiology B : Biology (1993), 17(3), 229-237

Various biological processes, such as photosensitization or inflammatory reactions, can generate singlet oxygen (O-1(2)) as one of the major oxidative species. Because this oxidant can be generated either ... [more ▼]

Various biological processes, such as photosensitization or inflammatory reactions, can generate singlet oxygen (O-1(2)) as one of the major oxidative species. Because this oxidant can be generated either extracellularly or intracellularly, it can cause severe damage to various biological macromolecules, even to those deeply embedded inside the cells such as DNA. Sublethal biological modifications induced by different DNA-damaging agents can promote various cellular responses initiated by the activation of various cellular genes and certain heterologous viruses. Since O-1(2) fulfils essential prerequisites for a genotoxic substance, we have examined the effects of an oxidative stress, mediated by this species, on cells harbouring a heterologous promoter-leader sequence derived from the human immunodeficiency virus type 1 (HIV-1). Our results demonstrate that HIV-1 long terminal repeat (LTR), integrated into the cellular I)NA of epithelial cells, can be transactivated following an oxidative stress mediated by O-1(2). In addition, using HIV-1 latently infected promonocytes or lymphocytes, it can be shown that virus reactivation can be induced through a sublethal dose of O-1(2) generated intracellularly. An extracellular generation of O-1(2) can promote a substantial lethal effect without HIV-1 reactivation. These data may be relevant to the understanding of the events converting a latent infection into a productive one and to the appearance of the acquired immune deficiency syndrome. [less ▲]

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See detailHIV-1 protease inhibitors do not interfere with provirus transcription and host cell apoptosis induced by combined treatment TNF-alpha plus TSA
Vandergeeten, Claire ULiege; Quivy, Vincent; Moutschen, Michel ULiege et al

in Biochemical Pharmacology (2007), 73(11), 1738-1748

HIV-1 latency represents a major hurdle to the complete eradication of the virus from patients under highly active anti-retroviral therapy (HAART) regimens. One solution to this problem would be to ... [more ▼]

HIV-1 latency represents a major hurdle to the complete eradication of the virus from patients under highly active anti-retroviral therapy (HAART) regimens. One solution to this problem would be to eliminate the latently infected cellular reservoirs by forcing gene expression in presence of HAART to prevent spreading of the infection by the newly synthesized viruses. Many studies have reported that a combination of a histone deacetylase inhibitor (HDACi) (i.e. TSA, NaBut, Valproic acid,...) with a pro-inflammatory cytokine (i.e. TNF alpha, IL-1,...) reactivates in a synergistic manner HIV-1 transcription in latently infected cells. The aim of the present study was to determine whether HIV-1 protease inhibitors (PIs) used in HAART (such as Saquinavir, Indinavir, Nelfinavir, Lopinavir, Ritonavir and Amprenavir) could interfere with the potential purge of the cellular reservoirs induced by a combined treatment involving TSA and TNF alpha. We showed, in two HIV-1 latently infected cell lines (ACH-2 and U1) that all PIs efficiently inhibited release of mature viral particles but did neither affect cell apoptosis nor NF-kappa B induction and HIV-1 transcription activation following combined treatment with TNF alpha + TSA. This study is encouraging in the fight against HIV-1 and shows that PIs should be compatible with an inductive adjuvent therapy for latent reservoir reduction/elimination in association with efficient HAART regimens. (c) 2007 Elsevier Inc. All rights reserved. [less ▲]

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See detailHIV-1 reactivation after an oxidative stress
Legrand, Sylvie ULiege; Vaira, Dolorès ULiege; Rentier, Bernard ULiege et al

in LinkVIII International Conference on AIDS/III STD World Congress, Amsterdam, the Netherlands 19-24 July 1992 (1992)

OBJECTIVES: A common denominator shared by several HIV-1 reactivation agents such as certain cytokines, UV irradiation and heat shock is their ability to cause stress response. Consequently, we have ... [more ▼]

OBJECTIVES: A common denominator shared by several HIV-1 reactivation agents such as certain cytokines, UV irradiation and heat shock is their ability to cause stress response. Consequently, we have investigated the effects of oxidative stress on HIV-1 reactivation, knowing that HIV-1 latently infected T cells can be exposed in vivo to such a stress when blood phagocytes are stimulated during inflammatory reactions. METHODS: The promonocytic (U1) and lymphocytic (ACH-2) cell lines, both HIV-1 chronically infected, were used to study the reactivation phenomenon. To test wether HIV-1 reactivation is mediated by LTR transactivation, the HeLa HIV-1 CAT cell line, which carries an integrated DNA cartridge containing CAT gene under control of HIV-1 LTR, was also exposed to an oxidative stress. RESULTS: Hydrogen peroxide exposure of U1 cells leads to an increased reverse transcriptase (RT) activity in supernatant fluid. Over the optimal concentrations range (0.5 to 1 mM), a four to fivefold stimulation level is reached. Below these concentrations, stress conditions are not sufficient and above, they induce a too important lethal effect. Immunofluorescence carried out on stressed U1 cells shows that H2O2 leads to HIV-1 gene expression activation and not to a release of viral particles from damaged cells. H2O2 also induces a stimulation of CAT activity in HeLa HIV-1 CAT cells. Intracellular singulet oxygen (1O2) is also able to induce an increase of RT activity in supernatant fluid of U1 and ACH-2 cells and a stimulation of CAT activity in HeLa HIV-1 CAT cells. A dose-response curve can also be demonstrated. In order to transpose these in vitro experiments to situations encountered in vivo, activated phagocytes were cocultivated with HeLa HIV-1 CAT cells. A weak stimulation of CAT activity was detected. CONCLUSIONS: Cellular oxidative damages induce HIV-1 LTR transactivation leading to viral gene expression and consequently to a burst of virus production. DNA damages induced by oxidative stress could be at the onset of HIV-1 reactivation. Experiments are now in progress to elucidate the mechanisms leading to HIV-1 reactivation after an oxidative stress. [less ▲]

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See detailHIV-1 reactivation after an oxidative stress
Legrand, Sylvie ULiege; Hoebeke, Maryse ULiege; Vaira, Dolorès ULiege et al

in Archives Internationales de Physiologie, de Biochimie et de Biophysique (1992), 100

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See detailHIV-1 regulation of latency in the monocyte-macrophage lineage and in CD4+ T lymphocytes.
Redel, Laetitia; Le Douce, Valentin; Cherrier, Thomas ULiege et al

in Journal of Leukocyte Biology (2010), 87(4), 575-88

The introduction in 1996 of the HAART raised hopes for the eradication of HIV-1. Unfortunately, the discovery of latent HIV-1 reservoirs in CD4+ T cells and in the monocyte-macrophage lineage proved the ... [more ▼]

The introduction in 1996 of the HAART raised hopes for the eradication of HIV-1. Unfortunately, the discovery of latent HIV-1 reservoirs in CD4+ T cells and in the monocyte-macrophage lineage proved the optimism to be premature. The long-lived HIV-1 reservoirs constitute a major obstacle to the eradication of HIV-1. In this review, we focus on the establishment and maintenance of HIV-1 latency in the two major targets for HIV-1: the CD4+ T cells and the monocyte-macrophage lineage. Understanding the cell-type molecular mechanisms of establishment, maintenance, and reactivation of HIV-1 latency in these reservoirs is crucial for efficient therapeutic intervention. A complete viral eradication, the holy graal for clinicians, might be achieved by strategic interventions targeting latently and productively infected cells. We suggest that new approaches, such as the combination of different kinds of proviral activators, may help to reduce dramatically the size of latent HIV-1 reservoirs in patients on HAART. [less ▲]

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See detailHIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays.
Vandenbroucke, Ina; Van Marck, Herwig; Mostmans, Wendy et al

in AIDS Research and Therapy (2010), 7

ABSTRACT : BACKGROUND : HIV-1 infected patients for whom standard gp160 phenotypic tropism testing failed are currently excluded from co-receptor antagonist treatment. To provide patients with maximal ... [more ▼]

ABSTRACT : BACKGROUND : HIV-1 infected patients for whom standard gp160 phenotypic tropism testing failed are currently excluded from co-receptor antagonist treatment. To provide patients with maximal treatment options, massively parallel sequencing of the envelope V3 domain, in combination with tropism prediction tools, was evaluated as an alternative tropism determination strategy. Plasma samples from twelve HIV-1 infected individuals with failing phenotyping results were available. The samples were submitted to massive parallel sequencing and to confirmatory recombinant phenotyping using a fraction of the gp120 domain. RESULTS : A cut-off for sequence reads interpretation of 5 to10 times the sequencing error rate (0.2%) was implemented. On average, each sample contained 7 different V3 haplotypes. V3 haplotypes were submitted to tropism prediction algorithms, and 4/14 samples returned with presence of a dual/mixed (D/M) tropic virus, respectively at 3%, 10%, 11%, and 95% of the viral quasispecies. V3 tropism prediction was confirmed by gp120 phenotyping, except for two out of 4 D/M predicted viruses (with 3 and 95%) which were phenotypically R5-tropic. In the first case, the result was discordant due to the limit of detection for the phenotyping technology, while in the latter case the prediction algorithms were not computing the viral tropism correctly. CONCLUSIONS : Although only demonstrated on a limited set of samples, the potential of the combined use of "deep sequencing + prediction algorithms" in cases where routine gp160 phenotype testing cannot be employed was illustrated. While good concordance was observed between gp120 phenotyping and prediction of R5-tropic virus, the results suggest that accurate prediction of X4-tropic virus would require further algorithm development. [less ▲]

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See detailHIV-related infections of the brain
Cuvelier, Marie-Laure ULiege; Leonard, Philippe ULiege; Rikir, Estelle ULiege et al

in Revue Médicale de Liège (2008), 63(5-6), 342-348

During the natural course of human immunodeficiency virus infection, central nervous system insults are very common. They can consist of infectious complications, consequently to the collapse of the ... [more ▼]

During the natural course of human immunodeficiency virus infection, central nervous system insults are very common. They can consist of infectious complications, consequently to the collapse of the patient's immune system. Alternatively, direct or indirect HIV-mediated lesions of cerebral vascular or neural cells can also occur. It is crucial to detect HIV-related infectious complications since their prognosis will depend on early and accurate treatments. The diagnosis is generally made by means of magnetic resonance imaging and lumbar puncture. [less ▲]

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See detailL'hiver de 1890-1891
Folie, François ULiege

in Bulletins de l'Académie Royale des Sciences, des Lettres et des Beaux-Arts de Belgique (1891), 3e série, t. 21(2), 160-166

The author summurizes the observations established during the winter of 1890-1891.

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See detailL'hiver, une force majeure?
Kohl, Benoît ULiege

Article for general public (2010)

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See detailHivernage de deux Tichodromes échelettes Tichodrama muraria en Wallonie en 2014-2015
Gailly, Robin ULiege; Mathelart, Charlotte

in Aves (2015), 52(4), 193-205

The Wallcreeper Tichodroma muraria is a rare wintering bird in Wallonia but is probably under detected. Specific research allowed finding a bird in Dinant on 30th December 2014. The wintering of that bird ... [more ▼]

The Wallcreeper Tichodroma muraria is a rare wintering bird in Wallonia but is probably under detected. Specific research allowed finding a bird in Dinant on 30th December 2014. The wintering of that bird was followed until its departure on 8th April 2015. The wintering range extended on a 2km-part of the Haute-Meuse valley including natural cliffs and buildings including the citadel. This article describes visited places, the roosting site and partial moult to the breeding plumage. A second wintering bird was found on 7th February 2015 in a quarry in the Ourthe valley and stayed until end of March. This is the first reported case of a simultaneous wintering of two Wallcreepers in Wallonia. A better prospecting of suitable sites could bring out wintering birds more regularly in Wallonia. [less ▲]

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See detailLes hivers de 1894-1895 et 1895-1896 en Belgique
Folie, François ULiege

in Bulletins de l'Académie Royale des Sciences, des Lettres et des Beaux-Arts de Belgique (1896), 3e série, t. 31(2), 136-147

The author summarizes and explains various observations made during the winters of 1894, 1895 and 1896 in Belgium.

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See detailHjelmslev
Badir, Sémir ULiege

Book published by Taishukan (2007)

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See detailHjelmslev
Badir, Sémir ULiege

Book published by Les Belles Lettres (2000)

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See detailHjelmslev's notion of "Participation"
Cigana, Lorenzo ULiege

Conference (2012, September 29)

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See detailThe HLA dermatosis connection
Nikkels, Arjen ULiege; Tassoudji, Nazli ULiege; Pierard, Gérald ULiege

in Journal of the European Academy of Dermatology & Venereology (1992), 1

A number of dermatological diseases are associated with distinct HLA types. These associations vary in different populations and ethnic groups. HLA determination can be related to different diseases ... [more ▼]

A number of dermatological diseases are associated with distinct HLA types. These associations vary in different populations and ethnic groups. HLA determination can be related to different diseases courses, various anatomical predilection sites and can be used as a diagnostic tool. However, the pathogenic role of HLA in susceptibility to specific dermatological diseases often remains unclear. [less ▲]

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See detailHLA genetics in 'latent' autoimmune diabetes of adults (LADA)
Geenen, Vincent ULiege

in International Diabetes Monitor (2008), 20

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See detailHLA-DQA is associated with abdominal aortic aneurysms in the Belgian population
Tromp, Gerard; Ogata, Toru; Grégoire, Lucie et al

in Annals of the New York Academy of Sciences (2006), 1085

Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs ... [more ▼]

Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with human leukocyte antigen (HLA) polymorphisms (HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles) in 387 AAA cases and 426 controls. We observed an association with the HLA-DQA1 locus among Belgian males, and found a significant difference in the HLA-DQA1 *0102 allele frequencies between AAA cases and controls. In conclusion, this study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs. [less ▲]

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See detailHLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis.
Ombrello, Michael J.; Remmers, Elaine F.; Tachmazidou, Ioanna et al

in Proceedings of the National Academy of Sciences of the United States of America (2015), 112(52), 15970-5

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether ... [more ▼]

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 x 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 x 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 x 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 x 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA. [less ▲]

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See detailHLA-driven convergence of HIV-1 viral subtypes B and F toward the adaptation to immune responses in human populations.
Dilernia, Dario Alberto; Jones, Leandro; Rodriguez, Sabrina ULiege et al

in PLoS ONE (2008), 3(10), 3429

BACKGROUND: Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a ... [more ▼]

BACKGROUND: Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naive HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. CONCLUSIONS: Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate. [less ▲]

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See detailHLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia
Baron, Frédéric ULiege; Maris, M. B.; Storer, B. E. et al

in Biology of Blood and Marrow Transplantation (2005), 11(4), 272-279

We evaluated 10/10 HLA antigen-matched unrelated hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning with fludarabine 3 x 30 mg/m(2) and 2 Gy of total body irradiation as ... [more ▼]

We evaluated 10/10 HLA antigen-matched unrelated hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning with fludarabine 3 x 30 mg/m(2) and 2 Gy of total body irradiation as treatment for patients with chronic myeloid leukemia who were ineligible for conventional HCT. Data from 21 consecutive patients in first chronic phase (CP1; n = 12), accelerated phase (AP; n = 5), second CP (CP2; n = 3), and blast crisis (n = 1) were analyzed. Stem cell sources were bone marrow (n = 4) or granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells (G-PBMCs; n = 17). The patient who underwent transplantation in blast crisis died on day 21 (too early to be evaluated. for engraftment) from progressive disease. Sustained engraftment was achieved in 5 of 12 patients who underwent transplantation in CP1, 4 of 5 patients who underwent transplantation in AP, and 2 of 3 patients who underwent transplantation in CP2, whereas 9 patients rejected their grafts between 28 and 400 days after HCT. Specifically, I of 4 marrow recipients and 10 of 17 G-PBMC recipients achieved sustained engraftment. Graft rejections were nonfatal in all cases and were followed by autologous reconstitution with persistence or recurrence of chronic myeloid leukemia. Seven of 11 patients with sustained engraftment-including all 5 patients in CP 1, 2 of 4 patients in AP, and neither of the 2 patients in CP2-were alive in complete cytogenetic remissions 118 to 1205 days (median, 867 days) after HCT. Two of the remaining 4 patients died of nonrelapse causes in complete (n = 1) or major (n = 1) cytogenetic remissions, and 2 died of progressive disease. Further efforts are directed at reducing the risk of graft rejection by exclusive use of G-PBMC and increasing the degree of pretransplantation immunosuppression. (c) 2005 American Society for Blood and Marrow Transplantation. [less ▲]

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