32 results on '"Matheux A"'
Search Results
2. Comparative Interleukin (IL)-2/Interferon (IFN)-γ and IL-4/IL-10 Responses during Acute Infection of Macaques Inoculated with Attenuated nef-Truncated or Pathogenic SIVmac251 Virus
- Author
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Benveniste, Olivier, Vaslin, Bruno, Le Grand, Roger, Cheret, Arnaud, Matheux, Franck, Theodoro, Frédéric, Cranage, Martin P., and Dormont, Dominique
- Published
- 1996
3. The Anti-Cancer Drug Dabrafenib Is a Potent Activator of the Human Pregnane X Receptor
- Author
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Nicolas Creusot, Matthieu Gassiot, Elina Alaterre, Barbara Chiavarina, Marina Grimaldi, Abdelhay Boulahtouf, Lucia Toporova, Sabine Gerbal-Chaloin, Martine Daujat-Chavanieu, Alice Matheux, Roger Rahmani, Céline Gongora, Alexandre Evrard, Philippe Pourquier, and Patrick Balaguer
- Subjects
dabrafenib ,hPXR ,colon and liver cancer cells ,proliferation ,Cytology ,QH573-671 - Abstract
The human pregnane X receptor (hPXR) is activated by a large set of endogenous and exogenous compounds and plays a critical role in the control of detoxifying enzymes and transporters regulating liver and gastrointestinal drug metabolism and clearance. hPXR is also involved in both the development of multidrug resistance and enhanced cancer cells aggressiveness. Moreover, its unintentional activation by pharmaceutical drugs can mediate drug–drug interactions and cause severe adverse events. In that context, the potential of the anticancer BRAF inhibitor dabrafenib suspected to activate hPXR and the human constitutive androstane receptor (hCAR) has not been thoroughly investigated yet. Using different reporter cellular assays, we demonstrate that dabrafenib can activate hPXR as efficiently as its reference agonist SR12813, whereas it does not activate mouse or zebrafish PXR nor hCAR. We also showed that dabrafenib binds to recombinant hPXR, induces the expression of hPXR responsive genes in colon LS174T-hPXR cancer cells and human hepatocytes and finally increases the proliferation in LS174T-hPXR cells. Our study reveals that by using a panel of different cellular techniques it is possible to improve the assessment of hPXR agonist activity for new developed drugs.
- Published
- 2020
- Full Text
- View/download PDF
4. Liquid Chromatography–High-Resolution Mass Spectrometry (LC–HRMS) Analysis Following Voluntary Carvedilol Poisoning in a Subject with Cirrhosis: A Case Report
- Author
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Berthier, Joseph, primary, Pasquet, Agathe, additional, Guerard, Pascal, additional, and Matheux, Alice, additional
- Published
- 2022
- Full Text
- View/download PDF
5. Liquid Chromatography–High-Resolution Mass Spectrometry (LC–HRMS) Analysis Following Voluntary Carvedilol Poisoning in a Subject with Cirrhosis: A Case Report.
- Author
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Berthier, Joseph, Pasquet, Agathe, Guerard, Pascal, and Matheux, Alice
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CARVEDILOL ,MASS spectrometry ,HOSPITAL admission & discharge ,CIRRHOSIS of the liver ,ATTEMPTED suicide ,RIBAVIRIN - Abstract
Accidental or intentional carvedilol poisoning is rarely reported. Here, we describe a case of attempted suicide with a large quantity of immediate-release carvedilol (75 mg) and alcohol. In order to determine the kinetics, liquid chromatography–high-resolution mass spectrometry analyses were performed. The results for the plasma concentration of carvedilol were 906 µg/L 3 h after ingestion, 288 µg/L 12 h after ingestion and 103 µg/L 24 h after ingestion. A one-compartment model with linear and first order best described the elimination of the carvedilol, and the estimated half-life was 5.8 h. The result 3 h after ingestion represented the highest concentration ever observed for this drug. However, the patient was cirrhotic, and liver function was impaired with decreased Factor V (45%) and prothrombin ratio (61%). These conditions may explain the high concentrations of carvedilol. The patient was treated with glucagon and discharged from the hospital the following day. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. PXR Modulates the Prostate Cancer Cell Response to Afatinib by Regulating the Expression of the Monocarboxylate Transporter SLC16A1
- Author
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Hanane Agherbi, Fanny Leenhardt, Litaty Mbatchi, Aurélie Garcin, Philippe Pourquier, Alexandre Evrard, Candice Marchive, Alice Matheux, Matthieu Gassiot, Nadine Houede, Abdelhay Boulahtouf, Gaëlle Fromont, Patrick Balaguer, Eve Combes, Céline Gongora, Eric Fabbrizio, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Gongora, Céline, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut du Cancer de Montpellier (ICM), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD)
- Subjects
0301 basic medicine ,Cancer Research ,Afatinib ,PXR ,[SDV]Life Sciences [q-bio] ,afatinib ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,digestive system ,Article ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Prostate ,medicine ,kinase inhibitors ,RC254-282 ,Pregnane X receptor ,Chemistry ,Kinase ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,biomarkers ,Dabrafenib ,medicine.disease ,prostate cancer ,[SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,digestive system diseases ,3. Good health ,Dasatinib ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,030220 oncology & carcinogenesis ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Cancer research ,SLC16A1 ,Erlotinib ,Biomakers ,medicine.drug - Abstract
Simple Summary Many kinase inhibitors have been tested as potential alternatives for the treatment of castration-resistant prostate cancers. However, none of these clinical trials led to drug approval despite interesting responses. Our study reveals that genes involved in drug metabolism and their master regulator PXR (Pregnane X Receptor) could be responsible, at least in part, for these disappointing results as they can modulate tumor cell response to specific kinase inhibitors. We found that stable expression of PXR sensitized prostate cancer cells to erlotinib, dabrafenib, and afatinib, while it rendered cells resistant to dasatinib and had no effect for other inhibitors tested. We also report for the first time that sensitization to afatinib is due to an alteration in drug transport that involves the SLC16A1 monocarboxylate transporter. Together, our results further indicate that PXR might be considered as a biomarker of response to kinase inhibitors in castration-resistant prostate cancers. Abstract Resistance to castration is a crucial issue in the treatment of metastatic prostate cancer. Kinase inhibitors (KIs) have been tested as potential alternatives, but none of them are approved yet. KIs are subject of extensive metabolism at both the hepatic and the tumor level. Here, we studied the role of PXR (Pregnane X Receptor), a master regulator of metabolism, in the resistance to KIs in a prostate cancer setting. We confirmed that PXR is expressed in prostate tumors and is more frequently detected in advanced forms of the disease. We showed that stable expression of PXR in 22Rv1 prostate cancer cells conferred a resistance to dasatinib and a higher sensitivity to erlotinib, dabrafenib, and afatinib. Higher sensitivity to afatinib was due to a ~ 2-fold increase in its intracellular accumulation and involved the SLC16A1 transporter as its pharmacological inhibition by BAY-8002 suppressed sensitization of 22Rv1 cells to afatinib and was accompanied with reduced intracellular concentration of the drug. We found that PXR could bind to the SLC16A1 promoter and induced its transcription in the presence of PXR agonists. Together, our results suggest that PXR could be a biomarker of response to kinase inhibitors in castration-resistant prostate cancers.
- Published
- 2021
7. PXR Modulates the Prostate Cancer Cell Response to Afatinib by Regulating the Expression of the Monocarboxylate Transporter SLC16A1
- Author
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Matheux, Alice, primary, Gassiot, Matthieu, additional, Fromont, Gaëlle, additional, Leenhardt, Fanny, additional, Boulahtouf, Abdelhay, additional, Fabbrizio, Eric, additional, Marchive, Candice, additional, Garcin, Aurélie, additional, Agherbi, Hanane, additional, Combès, Eve, additional, Evrard, Alexandre, additional, Houédé, Nadine, additional, Balaguer, Patrick, additional, Gongora, Céline, additional, Mbatchi, Litaty C., additional, and Pourquier, Philippe, additional
- Published
- 2021
- Full Text
- View/download PDF
8. The Anti-Cancer Drug Dabrafenib Is a Potent Activator of the Human Pregnane X Receptor
- Author
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Alexandre Evrard, Abdelhay Boulahtouf, Marina Grimaldi, Barbara Chiavarina, Matthieu Gassiot, Elina Alaterre, Alice Matheux, Céline Gongora, Lucia Toporova, Philippe Pourquier, Roger Rahmani, Sabine Gerbal-Chaloin, Nicolas Creusot, Martine Daujat-Chavanieu, Patrick Balaguer, LESUR, Hélène, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Swiss Federal Insitute of Aquatic Science and Technology [Dübendorf] (EAWAG)
- Subjects
0301 basic medicine ,Agonist ,medicine.drug_class ,proliferation ,[SDV]Life Sciences [q-bio] ,Antineoplastic Agents ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Oximes ,Constitutive androstane receptor ,medicine ,Humans ,dabrafenib ,lcsh:QH301-705.5 ,ComputingMilieux_MISCELLANEOUS ,Cell Proliferation ,Pregnane X receptor ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Activator (genetics) ,Chemistry ,Imidazoles ,Pregnane X Receptor ,Transporter ,Dabrafenib ,hPXR ,colon and liver cancer cells ,Hep G2 Cells ,General Medicine ,3. Good health ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Drug metabolism ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,HeLa Cells ,Protein Binding ,medicine.drug - Abstract
The human pregnane X receptor (hPXR) is activated by a large set of endogenous and exogenous compounds and plays a critical role in the control of detoxifying enzymes and transporters regulating liver and gastrointestinal drug metabolism and clearance. hPXR is also involved in both the development of multidrug resistance and enhanced cancer cells aggressiveness. Moreover, its unintentional activation by pharmaceutical drugs can mediate drug&ndash, drug interactions and cause severe adverse events. In that context, the potential of the anticancer BRAF inhibitor dabrafenib suspected to activate hPXR and the human constitutive androstane receptor (hCAR) has not been thoroughly investigated yet. Using different reporter cellular assays, we demonstrate that dabrafenib can activate hPXR as efficiently as its reference agonist SR12813, whereas it does not activate mouse or zebrafish PXR nor hCAR. We also showed that dabrafenib binds to recombinant hPXR, induces the expression of hPXR responsive genes in colon LS174T-hPXR cancer cells and human hepatocytes and finally increases the proliferation in LS174T-hPXR cells. Our study reveals that by using a panel of different cellular techniques it is possible to improve the assessment of hPXR agonist activity for new developed drugs.
- Published
- 2020
9. The Anti-Cancer Drug Dabrafenib Is a Potent Activator of the Human Pregnane X Receptor
- Author
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Creusot, Nicolas, primary, Gassiot, Matthieu, additional, Alaterre, Elina, additional, Chiavarina, Barbara, additional, Grimaldi, Marina, additional, Boulahtouf, Abdelhay, additional, Toporova, Lucia, additional, Gerbal-Chaloin, Sabine, additional, Daujat-Chavanieu, Martine, additional, Matheux, Alice, additional, Rahmani, Roger, additional, Gongora, Céline, additional, Evrard, Alexandre, additional, Pourquier, Philippe, additional, and Balaguer, Patrick, additional
- Published
- 2020
- Full Text
- View/download PDF
10. Comparative interleukin (IL)-2/interferon (IFN)-gamma and IL-4/IL-10 responses during acute infection of macaques inoculated with attenuated nef-truncated or pathogenic SIVmac251 virus
- Author
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Benveniste, Olivier, Vaslin, Bruno, Le Grand, Roger, Cheret, Arnaud, Matheux, Franck, Theodoro, Frederic, Cranage, Martin P., and Dormont, Dominique
- Subjects
Interleukins -- Research ,Interferon gamma -- Research ,Macaques -- Research ,Pathogenic microorganisms -- Research ,Immunodeficiency -- Research ,Science and technology - Abstract
Comparison of immune responses to infection by a pathogenic or a nonpathogenic immunodeficiency virus in macaques may provide insights into pathogenetic events leading to simian AIDS. This work is aimed at exploring cytokine expression during infection by simian immunodeficiency virus (SIV). We used semiquantitative reverse transcription-PCR to monitor interleukin (IL)-2/interferon (IFN)-[Gamma] (Th1-like), and IL-4/IL-10 (Th2-like) expression in unmanipulated peripheral blood mononuclear cells (PBMCs), during the acute phase of infection of eight cynomolgus macaques (Macaca fascicularis) with a pathogenic primary isolate of SIVmac251 (full-length nef), and of four other cynomolgus macaques by an attenuated molecular clone of SIVmac251 (nef-truncated). All the monkeys became infected, as clearly shown by the presence of infected PBMCs and by seroconversion. Nevertheless, PBMC-associated virus loads and p27 antigenemia in monkeys infected by the attenuated virus clone remained lower than those observed in animals infected with the pathogenic SIVmac251 isolate. A rise of IL-10 mRNA expression occurred in both groups of monkeys coincident with the peak of viral replication. In monkeys infected with the pathogenic SIVmac251, IL-2, IL-4, and IFN-[Gamma] mRNAs were either weakly detectable or undetectable. On the contrary, animals infected by the attenuated virus exhibited an overexpression of these cytokine mRNAs during the first weeks after inoculation. The lack of expression of these cytokines in monkeys infected with the pathogenic primary isolate may reflect early immunodeficiency.
- Published
- 1996
11. Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251
- Author
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Dormont Dominique, Rousseau Véronique, Peyramaure Sophie, Matheux Franck, Larghero Jérome, Boson Bertrand, Lauret Evelyne, Gay Wilfried, De Maeyer Edward, and Le Grand Roger
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251. Results Two groups of three animals infected for more than one year with a pathogenic primary isolate of SIVmac251 were included in this study. The macaques received three infusions of their own lymphocytes transduced ex vivo with the construct encoding macaque IFN-β (MaIFN-β or with a vector carrying a version of the MaIFN-β gene with a deletion preventing translation of the mRNA. Cellular or plasma viremia increased transiently following injection in most cases, regardless of the retroviral construct used. Transduced cells were detected only transiently after each infusion, among the peripheral blood mononuclear cells of all the animals, with copy numbers of 10 to 1000 per 106 peripheral mononuclear cells. Conclusion Long-term follow-up indicated that the transitory presence of such a small number of cells producing such small amounts of MaIFN-β did not prevent animals from the progressive decrease in CD4+ cell count typical of infection with simian immunodeficiency virus. These results reveal potential pitfalls for future developments of gene therapy strategies of HIV infection.
- Published
- 2004
- Full Text
- View/download PDF
12. RANTES, IFN-γ, CCR1, and CCR5 mRNA Expression in Peripheral Blood, Lymph Node, and Bronchoalveolar Lavage Mononuclear Cells during Primary Simian Immunodeficiency Virus Infection of Macaques
- Author
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Chéret, Arnaud, Le Grand, Roger, Caufour, Philippe, Neildez, Olivier, Matheux, Franck, Théodoro, Frédéric, Vaslin, Bruno, and Dormont, Dominique
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- 1999
- Full Text
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13. Direct Genetic Correction as a New Method for Diagnosis and Molecular Characterization of MHC Class II Deficiency
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Aydan Ikinciogullari, David A. Zapata, Walter Reith, Madeleine Zufferey, Franck Matheux, José R. Regueiro, Figen Dogu, Emmanuèle Barras, and Jean Villard
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Male ,RFXANK ,T-Lymphocytes ,Genetic Vectors ,Molecular Sequence Data ,Immunologic Deficiency Syndromes/classification/ diagnosis/ genetics/pathology ,Regulatory Factor X Transcription Factors ,chemical and pharmacologic phenomena ,ddc:616.07 ,Biology ,Histocompatibility Antigens Class II/ analysis/genetics ,Cell Line ,Viral vector ,Transduction, Genetic ,Drug Discovery ,medicine ,CIITA ,Genetics ,Humans ,Amino Acid Sequence ,Gene ,Molecular Biology ,Trans-Activators/ genetics/metabolism ,Transcription Factors/ genetics/metabolism ,Pharmacology ,Base Sequence ,Genetic heterogeneity ,Lentivirus/genetics ,Lentivirus ,Genetic Complementation Test ,Histocompatibility Antigens Class II ,Immunologic Deficiency Syndromes ,Bare lymphocyte syndrome ,Nuclear Proteins ,Reproducibility of Results ,Genetic Therapy ,Gene Therapy ,T-Lymphocytes/metabolism ,medicine.disease ,DNA-Binding Proteins ,DNA-Binding Proteins/ genetics/metabolism ,Genetic Vectors/genetics ,Trans-Activators ,Primary immunodeficiency ,Molecular Medicine ,Female ,RFX5 ,Transcription Factors - Abstract
Major histocompatibility complex class II (MHCII) deficiency is a primary immunodeficiency resulting from defects in one of four different MHCII-specific transcription factors-CIITA, RFX5, RFXAP, and RFXANK. Despite this genetic heterogeneity, the phenotypical manifestations are homogeneous. It is frequently difficult to establish a definitive diagnosis of the disease on the basis of clinical and immunological criteria. Moreover, the phenotypical homogeneity precludes unambiguous identification of the regulatory gene that is affected. Identification of the four genes mutated in the disease has now allowed us to develop a rapid and straightforward diagnostic test for new MHCII-deficiency patients. This test is based on direct correction of the genetic defect by transduction of cells from patients with lentiviral vectors encoding CIITA, RFXANK, RFX5, or RFXAP. We have validated this approach by defining the molecular defects in two new patients. The RFXANK vector restored MHCII expression in a T cell line from one patient. The RFXAP vector corrected primary cells (PBL) from a second patient. Molecular analysis confirmed the presence of homozygous mutations in the RFXANK and RFXAP genes, respectively. Direct genetic correction represents a valuable tool for the diagnosis and classification of new MHCII-deficiency patients.
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- 2002
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14. RANTES, IFN-γ, CCR1, and CCR5 mRNA Expression in Peripheral Blood, Lymph Node, and Bronchoalveolar Lavage Mononuclear Cells during Primary Simian Immunodeficiency Virus Infection of Macaques
- Author
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O. Neildez, P Caufour, F Matheux, R Le Grand, Frédéric Théodoro, Dominique Dormont, Arnaud Chéret, and Bruno Vaslin
- Subjects
Chemokine ,Receptors, CCR5 ,T cell ,animal diseases ,viruses ,Receptors, CCR1 ,Simian Acquired Immunodeficiency Syndrome ,Biology ,medicine.disease_cause ,Bronchoalveolar Lavage ,Peripheral blood mononuclear cell ,Interferon-gamma ,Immune system ,T-Lymphocyte Subsets ,Virology ,medicine ,Animals ,RNA, Messenger ,Primary isolate ,Chemokine CCL5 ,virus diseases ,Simian immunodeficiency virus ,biology.organism_classification ,Kinetics ,Macaca fascicularis ,medicine.anatomical_structure ,Gene Expression Regulation ,Viral replication ,Immunology ,Lentivirus ,Leukocytes, Mononuclear ,biology.protein ,Female ,Receptors, Chemokine ,Simian Immunodeficiency Virus ,Lymph Nodes ,Follow-Up Studies - Abstract
Primary infection of macaques with pathogenic isolates of simian immunodeficiency virus (SIV) (as a model of HIV infection in humans) represents a unique opportunity to study early lentivirus/host interactions. We sought to determine whether there is a temporal relationship linking SIV replication and dissemination and the expression of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) and the SIV/HIV coreceptor CCR5 in different tissues during acute SIV infection of macaques. Four cynomolgus macaques were inoculated intravenously with a pathogenic primary isolate of SIVmac251. RT-PCR was used to monitor the expression of RANTES and CCR5 mRNA in fresh isolated mononuclear cells from blood, lymph node, and bronchoalveolar lavages. These expressions were compared to those of IFN-γ as an indicator of the development of the immune response and to another receptor for RANTES, CCR1, which is not described as a coreceptor for SIV/HIV-1 entry. An enhancement of CCR1/CCR5 mRNA expression was noticed during primary SIVmac251 infection of macaques, mainly in tissue. In the three different compartments investigated, IFN-γ and RANTES overexpression was noticed by the time of systemic viral replication containment. Our results put CCR5 and RANTES mRNA expression back in the context of inflammatory and immune responses to SIV primary infection.
- Published
- 1999
- Full Text
- View/download PDF
15. Macaque Lymphocytes Transduced by a Constitutively Expressed Interferon beta Gene Display an Enhanced Resistance to SIVmac251 Infection
- Author
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Edward De Maeyer, Véronique Rousseau, Dominique Dormont, Roger Le Grand, Evelyne Lauret, and F Matheux
- Subjects
Time Factors ,Transgene ,Genetic enhancement ,Genetic Vectors ,Molecular Sequence Data ,Simian Acquired Immunodeficiency Syndrome ,Lymphocyte proliferation ,Macaque ,3T3 cells ,Viral vector ,Mice ,Transduction (genetics) ,Transduction, Genetic ,biology.animal ,Genetics ,medicine ,Animals ,Humans ,Lymphocytes ,Molecular Biology ,Gene ,Immunity, Cellular ,Base Sequence ,Dose-Response Relationship, Drug ,Sequence Homology, Amino Acid ,biology ,3T3 Cells ,Genetic Therapy ,Interferon-beta ,Virology ,Gene Products, rex ,Macaca fascicularis ,Phenotype ,Retroviridae ,medicine.anatomical_structure ,Molecular Medicine ,Simian Immunodeficiency Virus ,Cell Division - Abstract
We are developing a method of gene therapy of HIV infection based on the low constitutive expression of an interferon beta (IFN-beta) gene in HIV target cells. Herein we report the first step in the development of a relevant animal model, provided by the macaque (Macaca fascicularis) infected with a pathogenic SIVmac251 isolate. To avoid the possibility of in vivo rejection of macaque lymphocytes expressing Hu IFN-beta, we have PCR-amplified and sequenced the Ma IFN-beta-coding sequence, and placed it under the control of a PstI-NruI 0.6-kb fragment of the murine H-2Kb gene promoter in the MFG-K(b)MaIFNbeta retroviral vector. Lymphocytic CEMX174 cells, transduced by coculture on packaging cells with this construct, harbored a mean of 0.07 to 1.2 copies of the IFN-beta transgene per cell, and were characterized by an IFN production ranging from 75 to 750 units per 5 x 10(5) cells per 3 days. The IFN-beta-transduced populations displayed an enhanced resistance against the pathogenic SIVmac251 isolate. Control experiments showed that the enhanced resistance could not be ascribed to the Ma IFN-beta released during the 3 days of coculture by the packaging cells, or to the mere transduction with a retroviral vector. Macaque lymphocytes transduced by the MFG-K(b)MaIFNbeta retroviral vector by coculture on packaging cells, acquired a mean number of IFN-beta transgene copies per cell ranging from 0.03 to 0.1. Such transduction led to the release of IFN-beta into the culture medium, ranging from 10 to 20 units per 5 x 10(5) cells per 3 days. This increased the anti-SIV resistance of the lymphocytes, as demonstrated by a decreased p27 antigen release into the culture medium, without affecting lymphocyte proliferation.
- Published
- 1999
16. O017: A novel antiviral technology for air filtration
- Author
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T Pelet and F Matheux
- Subjects
Microbiology (medical) ,Air filtration ,Potential impact ,Indoor bioaerosol ,Public Health, Environmental and Occupational Health ,INFECTIOUS PROCESS ,Biology ,Virology ,Microbiology ,Spore ,Human health ,Infectious Diseases ,Susceptible individual ,Oral Presentation ,Pharmacology (medical) ,Desiccation - Abstract
Bioaerosols exposure and potential impact on human health is a growing concern. Bioaerosols are assemblies of particles of variable biological origin (bacterial, viral, or fungal) suspended in the air and capable of initiating an infectious process in a susceptible host. They usually consist of a mixture of mono-dispersed and aggregate cells, spores, or viruses, carried by other materials, such as respiratory secretions. With rapid desiccation, the resultant smaller aerosols can remain airborne longer, while larger aerosols may initially fall out and then become re-suspended after desiccation.
- Published
- 2013
17. Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251
- Author
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Wilfried, Gay, Evelyne, Lauret, Bertrand, Boson, Jérome, Larghero, Franck, Matheux, Sophie, Peyramaure, Véronique, Rousseau, Dominique, Dormont, Edward, De Maeyer, Roger, Le Grand, Laboratoire d'Immuno-Pathologie Expérimentale, Service de Neurovirologie, Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CRSSA, Hematopoïèse et Cellules Souches (U362), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Maylin, Françoise, and Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)
- Subjects
Male ,lcsh:Immunologic diseases. Allergy ,MESH: DNA Primers ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,MESH: CD4 Lymphocyte Count ,Genetic Vectors ,Simian Acquired Immunodeficiency Syndrome ,CD8-Positive T-Lymphocytes ,MESH: Base Sequence ,MESH: Genetic Vectors ,Animals ,MESH: Animals ,MESH: Promoter ,Lymphocytes ,Promoter Regions, Genetic ,DNA Primers ,Sequence Deletion ,MESH: Acquired Immunodeficiency Syndrome ,Acquired Immunodeficiency Syndrome ,Base Sequence ,MESH: Interferon-beta ,Research ,Genetic Therapy ,Interferon-beta ,Viral Load ,MESH: CD8-Positive T-Lymphocytes ,MESH: Male ,CD4 Lymphocyte Count ,MESH: DNA, Viral ,Macaca fascicularis ,Retroviridae ,MESH: Macaca fascicularis ,Lymphocyte Transfusion ,DNA, Viral ,MESH: Lymphocyte Transfusion ,RNA, Viral ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Simian Immunodeficiency Virus ,MESH: Lymphocytes ,MESH: Gene Therapy ,lcsh:RC581-607 - Abstract
Background The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251. Results Two groups of three animals infected for more than one year with a pathogenic primary isolate of SIVmac251 were included in this study. The macaques received three infusions of their own lymphocytes transduced ex vivo with the construct encoding macaque IFN-β (MaIFN-β or with a vector carrying a version of the MaIFN-β gene with a deletion preventing translation of the mRNA. Cellular or plasma viremia increased transiently following injection in most cases, regardless of the retroviral construct used. Transduced cells were detected only transiently after each infusion, among the peripheral blood mononuclear cells of all the animals, with copy numbers of 10 to 1000 per 106 peripheral mononuclear cells. Conclusion Long-term follow-up indicated that the transitory presence of such a small number of cells producing such small amounts of MaIFN-β did not prevent animals from the progressive decrease in CD4+ cell count typical of infection with simian immunodeficiency virus. These results reveal potential pitfalls for future developments of gene therapy strategies of HIV infection.
- Published
- 2004
18. Cellular and gene therapy for major histocompatibility complex class II deficiency
- Author
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Jean Villard and Franck Matheux
- Subjects
Genetics ,Major Histocompatibility Complex Class II ,Physiology ,Genetic enhancement ,Histocompatibility Antigens Class II ,chemical and pharmacologic phenomena ,Disease ,Human leukocyte antigen ,Genetic Therapy ,Biology ,medicine.disease ,Major histocompatibility complex ,Immunology ,Minor histocompatibility antigen ,Primary immunodeficiency ,medicine ,biology.protein ,Animals ,Humans ,Severe Combined Immunodeficiency ,Gene - Abstract
Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency. Lentiviral vectors are used for gene therapy in a mouse model of this disease. In addition, by a direct genetic correction approach, a diagnostic test to determine which of the four MHC II genes is defective in new MHC II-deficiency patients has been optimized.
- Published
- 2004
19. Simian immunodeficiency virus resistance of macaques infused with interferon beta-engineered lymphocytes
- Author
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Jérôme Larghero, F Matheux, Véronique Rousseau, Bertrand Boson, Bruno Vaslin, Roger Legrand, Edward De Maeyer, Dominique Dormont, E Lauret, and Arnaud Chéret
- Subjects
Genetic enhancement ,Cell ,Genetic Vectors ,Simian Acquired Immunodeficiency Syndrome ,Biology ,medicine.disease_cause ,Transfection ,Macaque ,Viral vector ,In vivo ,Interferon ,Virology ,biology.animal ,medicine ,Animals ,Lymphocytes ,Interferon-beta ,Simian immunodeficiency virus ,medicine.anatomical_structure ,Retroviridae ,Immunology ,Macaca ,Simian Immunodeficiency Virus ,Immunotherapy ,CD8 ,medicine.drug - Abstract
To test thein vivoanti-simian immunodeficiency virus (SIV) efficacy of interferon (IFN)-β-engineered lymphocytes, peripheral blood lymphocytes harvested from two uninfected macaques were transduced with a retroviral vector carrying a constitutively expressed IFN-β gene and reinfused, resulting in approximately 1 IFN-β-transduced cell out of 1000 circulating cells. The gene-modified cells were well tolerated and could be detected for at least 74 days without causing any apparent side effects. These two animals together with three untreated control macaques were then infected with SIVmac251. The two IFN-β-infused macaques are in good health, 478 days after infection, with a reduced plasma virus load and sustained numbers of CD4+and CD8+cells. Throughout the study, the proportion of IFN-β-transduced cells has been maintained. Of the three control macaques, two were characterized by a high plasma virus load and a decrease in CD4+cells. One was moribund and was sacrificed 350 days after infection and the other now has fewer than 100 circulating CD4+cells/ml. Unexpectedly, the third control macaque, which, like the two IFN-β-infused animals, had a low plasma virus load and a maintenance of CD4+and CD8+cell number, was characterized by a permanent level of serum IFN-β, of unknown origin, already present before SIV infection. Although no definite conclusion can be made in view of the limited number of animals, these data indicate that further exploration is warranted of an IFN-β-based anti-human immunodeficiency virus gene therapy.
- Published
- 2000
20. Selective quasispecies transmission after systemic or mucosal exposure of macaques to simian immunodeficiency virus
- Author
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F Matheux, Arnaud Chéret, P Caufour, Roger Le Grand, O. Neildez, Bruno Vaslin, Dominique Dormont, Frédéric Théodoro, and Pierre Roques
- Subjects
Sexual transmission ,Molecular Sequence Data ,Simian Acquired Immunodeficiency Syndrome ,Viremia ,Viral quasispecies ,Biology ,HIV Envelope Protein gp120 ,medicine.disease_cause ,Virus Replication ,Peripheral blood mononuclear cell ,Viral envelope ,Viral Envelope Proteins ,Virology ,medicine ,Animals ,Amino Acid Sequence ,Seroconversion ,Intestinal Mucosa ,Phylogeny ,Membrane Glycoproteins ,Transmission (medicine) ,Simian immunodeficiency virus ,medicine.disease ,Immunology ,Vagina ,Macaca ,Female ,Simian Immunodeficiency Virus - Abstract
Sexual transmission is the major cause of the AIDS epidemic. For the development of new antiviral and vaccine strategies, we therefore need to understand the mechanisms by which lentiviruses cross the mucosal barrier and the subsequent pathogenic consequences. For this purpose, experimental approaches are greatly facilitated by the development of relevant animal models. In this study, macaques were inoculated intravenously, intrarectally, or intravaginally with a pathogenic cell-free isolate of SIVmac251. Patterns of virological and immunological events significantly differed between vaginally (transient viremia, late seroconversion) and intravenously or intrarectally inoculated monkeys (persistent viremia and early seroconversion). Two weeks after infection, analysis of the env gene nucleotide sequences of proviruses recovered from PBMCs demonstrated that most of the differences were observed in the V1 loop. Three viral variants were specifically associated with vaginal transmission, whereas no such selection was evidenced after intravenous or intrarectal transmissions. These results are in favor of specific mechanisms associated with vaginal transmission, implicating viral envelope structure.
- Published
- 1998
21. O017: A novel antiviral technology for air filtration
- Author
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Pelet, T, primary and Matheux, F, additional
- Published
- 2013
- Full Text
- View/download PDF
22. Superinfection of HIV-2-preinfected macaques after rectal exposure to a primary isolate of SIVmac251
- Author
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Arnaud Chéret, F Matheux, Dominique Dormont, Pierre Roques, Bruno Vaslin, Isabelle Nicol-Jourdain, Lahcen Wakrim, Roger Le Grand, and Frédéric Théodoro
- Subjects
Male ,animal diseases ,viruses ,Molecular Sequence Data ,HIV Infections ,Biology ,HIV Antibodies ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Cell Line ,T-Lymphocyte Subsets ,Virology ,medicine ,Animals ,Humans ,Primary isolate ,Cells, Cultured ,AIDS Vaccines ,Base Sequence ,Antibody titer ,Rectum ,virus diseases ,Simian immunodeficiency virus ,Provirus ,Cell culture ,Superinfection ,DNA, Viral ,HIV-2 ,biology.protein ,Leukocytes, Mononuclear ,Macaca ,Female ,Simian Immunodeficiency Virus ,Antibody - Abstract
To test the protection afforded by a weakly pathogenic HIV-2 isolate against the superinfection or development of SIV-induced disease, we intrarectally challenged six HIV-2-preinfected rhesus monkeys with a pathogenic isolate of SIVmac251. At the time of SIV challenge, none of these HIV-2-infected animals was positive for virus isolation, p27-Gag antigenemia, or HIV-2 provirus detection in PBMCs or peripheral lymph nodes. However, all monkeys exhibited anti-HIV-2 antibody titers ranging from 102to 103. Neutralizing antibodies against the challenge SIV strain were also detected in two animals. After rectal exposure to SIVmac251, five of the six HIV-2-preinfected macaques were superinfected. SIVmac251 DNA sequences were detected repeatedly in the PBMCs of the five superinfected animals and the two controls, whereas no HIV-2 provirus was detected for 14 months postchallenge. The one monkey that resisted superinfection was negative for all SIV infection criteria. This monkey exhibited the highest anti-SIV ELISA and cross-neutralizing antibody titers on the day of SIV challenge. Preinfection with a weakly pathogenic HIV-2 ROD isolate protected one of six macaques from infection with the closely related pathogenic SIVmac251 isolate, but no protection from the progression of disease was evidenced in the other five.
- Published
- 1996
23. Comparative interleukin (IL-2)/interferon IFN-gamma and IL-4/IL-10 responses during acute infection of macaques inoculated with attenuated nef-truncated or pathogenic SICmac251 virus
- Author
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Martin Cranage, Arnaud Chéret, Frédéric Théodoro, Olivier Benveniste, R. Le Grand, Bruno Vaslin, F Matheux, and Dominique Dormont
- Subjects
viruses ,CD4-CD8 Ratio ,Simian Acquired Immunodeficiency Syndrome ,Gene Expression ,Biology ,medicine.disease_cause ,Antibodies, Viral ,Virus ,Interferon-gamma ,Interferon ,T-Lymphocyte Subsets ,medicine ,Animals ,RNA, Messenger ,Primary isolate ,Immunodeficiency ,Multidisciplinary ,Attenuated vaccine ,Interleukin ,Simian immunodeficiency virus ,medicine.disease ,Virology ,Genes, nef ,Interleukin-10 ,Macaca fascicularis ,Simian AIDS ,Acute Disease ,Leukocytes, Mononuclear ,Cytokines ,Interleukin-2 ,Simian Immunodeficiency Virus ,Interleukin-4 ,medicine.drug ,Research Article - Abstract
Comparison of immune responses to infection by a pathogenic or a nonpathogenic immunodeficiency virus in macaques may provide insights into pathogenetic events leading to simian AIDS. This work is aimed at exploring cytokine expression during infection by simian immunodeficiency virus (SIV). We used semiquantitative reverse transcription-PCR to monitor interleukin (IL)-2/interferon (IFN)-gamma (Th1-like), and IL-4/IL-10 (Th2-like) expression in unmanipulated peripheral blood mononuclear cells (PBMCs), during the acute phase of infection of eight cynomolgus macaques (Macaca fascicularis) with a pathogenic primary isolate of SIVmac251 (full-length nef), and of four other cynomolgus macaques by an attenuated molecular clone of SIVmac251 (nef-truncated). All the monkeys became infected, as clearly shown by the presence of infected PBMCs and by seroconversion. Nevertheless, PBMC-associated virus loads and p27 antigenemia in monkeys infected by the attenuated virus clone remained lower than those observed in animals infected with the pathogenic SIVmac251 isolate. A rise of IL-10 mRNA expression occurred in both groups of monkeys coincident with the peak of viral replication. In monkeys infected with the pathogenic SIVmac251, IL-2, IL-4, and IFN-gamma mRNAs were either weakly detectable or undetectable. On the contrary, animals infected by the attenuated virus exhibited an overexpression of these cytokine mRNAs during the first weeks after inoculation. The lack of expression of these cytokines in monkeys infected with the pathogenic primary isolate may reflect early immunodeficiency.
- Published
- 1996
24. Cellular and Gene Therapy for Major Histocompatibility Complex Class II Deficiency
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Matheux, Franck, primary and Villard, Jean, additional
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- 2004
- Full Text
- View/download PDF
25. Direct Genetic Correction as a New Method for Diagnosis and Molecular Characterization of MHC Class II Deficiency
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Matheux, Franck, primary, Ikinciogullari, Aydan, additional, Zapata, David A., additional, Barras, Emmanuèle, additional, Zufferey, Madeleine, additional, Dogu, Figen, additional, Regueiro, José R., additional, Reith, Walter, additional, and Villard, Jean, additional
- Published
- 2002
- Full Text
- View/download PDF
26. [Untitled]
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Wilfried Gay, Evelyne Lauret, Bertrand Boson, Jérome Larghero, Franck Matheux, Sophie Peyramaure, Véronique Rousseau, Dominique Dormont, Edward De Maeyer, and Roger Le Grand
- Subjects
0303 health sciences ,biology ,Genetic enhancement ,Simian immunodeficiency virus ,medicine.disease_cause ,Macaque ,Virology ,3. Good health ,Viral vector ,03 medical and health sciences ,Transduction (genetics) ,0302 clinical medicine ,Infectious Diseases ,Interferon-beta production ,030220 oncology & carcinogenesis ,biology.animal ,Immunology ,medicine ,biology.protein ,Antibody ,Autocrine signalling ,030304 developmental biology - Abstract
Background The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251.
- Published
- 2004
27. Simian immunodeficiency virus resistance of macaques infused with interferon β-engineered lymphocytes
- Author
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Matheux, Franck, primary, Lauret, Evelyne, additional, Rousseau, Véronique, additional, Larghero, Jérôme, additional, Boson, Bertrand, additional, Vaslin, Bruno, additional, Cheret, Arnaud, additional, De Maeyer, Edward, additional, Dormont, Dominique, additional, and LeGrand, Roger, additional
- Published
- 2000
- Full Text
- View/download PDF
28. Macaque Lymphocytes Transduced by a Constitutively Expressed Interferon beta Gene Display an Enhanced Resistance to SIVmac251 Infection
- Author
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Matheux, Franck, primary, Grand, Roger Le, additional, Rousseau, Veronique, additional, Maeyer, Edward De, additional, Dormont, Dominique, additional, and Lauret, Evelyne, additional
- Published
- 1999
- Full Text
- View/download PDF
29. Selective Quasispecies Transmission after Systemic or Mucosal Exposure of Macaques to Simian Immunodeficiency Virus
- Author
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Neildez, Olivier, primary, Le Grand, Roger, additional, Caufour, Philippe, additional, Vaslin, Bruno, additional, Chéret, Arnaud, additional, Matheux, Franck, additional, Théodoro, Frédéric, additional, Roques, Pierre, additional, and Dormont, Dominique, additional
- Published
- 1998
- Full Text
- View/download PDF
30. Superinfection of HIV-2-Preinfected Macaques after Rectal Exposure to a Primary Isolate of SIVmac251
- Author
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WAKRIM, LAHCEN, primary, LE GRAND, ROGER, additional, VASLIN, BRUNO, additional, CHÉRET, ARNAUD, additional, MATHEUX, FRANCK, additional, THEODORO, FREDERIC, additional, ROQUES, PIERRE, additional, NICOL-JOURDAIN, ISABELLE, additional, and DORMONT, DOMINIQUE, additional
- Published
- 1996
- Full Text
- View/download PDF
31. Cellular and gene therapy for major histocompatibility complex class II deficiency.
- Author
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Matheux Franck and Villard Jean
- Subjects
- *
MAJOR histocompatibility complex , *IMMUNOGENETICS , *IMMUNODEFICIENCY , *GENE therapy , *GENES - Abstract
Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency. Lentiviral vectors are used for gene therapy in a mouse model of this disease. In addition, by a direct genetic correction approach, a diagnostic test to determine which of the four MHC II genes is defective in new MHC II-deficiency patients has been optimized. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
32. Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251.
- Author
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Gay, Wilfried, Lauret, Evelyne, Boson, Bertrand, Larghero, Jérome, Matheux, Franck, Peyramaure, Sophie, Rousseau, Véronique, Dormont, Dominique, De Maeyer, Edward, and Le Grand, Roger
- Subjects
AIDS ,INTERFERONS ,LYMPHOCYTES ,MACAQUES ,MESSENGER RNA ,GENE therapy - Abstract
Background: The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251. Results: Two groups of three animals infected for more than one year with a pathogenic primary isolate of SIVmac251 were included in this study. The macaques received three infusions of their own lymphocytes transduced ex vivo with the construct encoding macaque IFN-β (MaIFN-β or with a vector carrying a version of the MaIFN-β gene with a deletion preventing translation of the mRNA. Cellular or plasma viremia increased transiently following injection in most cases, regardless of the retroviral construct used. Transduced cells were detected only transiently after each infusion, among the peripheral blood mononuclear cells of all the animals, with copy numbers of 10 to 1000 per 10
6 peripheral mononuclear cells. Conclusion: Long-term follow-up indicated that the transitory presence of such a small number of cells producing such small amounts of MaIFN-β did not prevent animals from the progressive decrease in CD4+ cell count typical of infection with simian immunodeficiency virus. These results reveal potential pitfalls for future developments of gene therapy strategies of HIV infection. [ABSTRACT FROM AUTHOR]- Published
- 2004
- Full Text
- View/download PDF
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