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18 results on '"MESH: Receptors, CCR5"'

1. THETA

Author

Nicolas Jeanne, Caroline Lefebvre, Pierre Delobel, Romain Carcenac, Florence Nicot, Chloé Dimeglio, Stéphanie Raymond, Christelle Reynes, Michelle Cazabat, Jacques Izopet, Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [Toulouse], and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]

Subjects
Statistics and Probability, Receptors, CXCR4, Silver, Genotype, Receptors, CCR5, MESH: HIV-1, viruses, Human immunodeficiency virus (HIV), HIV Infections, Computational biology, MESH: HIV Infections, MESH: Receptors, CCR5, HIV Envelope Protein gp120, Biology, Gp41, medicine.disease_cause, Biochemistry, MESH: Receptors, CXCR4, MESH: Genotype, MESH: HIV Envelope Protein gp120, 03 medical and health sciences, Data sequences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Silver, medicine, Molecular Biology, Tropism, 030304 developmental biology, 0303 health sciences, 030306 microbiology, virus diseases, 3. Good health, Computer Science Applications, Europe, Viral Tropism, Computational Mathematics, Computational Theory and Mathematics, GenBank, HIV-1, Tissue tropism, MESH: Europe, MESH: Viral Tropism, Selection operator
Abstract

Motivation The circulating recombinant form of HIV-1 CRF02-AG is the most frequent non-B subtype in Europe. Anti-HIV therapy and pathophysiological studies on the impact of HIV-1 tropism require genotypic determination of HIV-1 tropism for non-B subtypes. But genotypic approaches based on analysis of the V3 envelope region perform poorly when used to determine the tropism of CRF02-AG. We, therefore, designed an algorithm based on information from the gp120 and gp41 ectodomain that better predicts the tropism of HIV-1 subtype CRF02-AG. Results We used a bio-statistical method to identify the genotypic determinants of CRF02-AG coreceptor use. Toulouse HIV Extended Tropism Algorithm (THETA), based on a Least Absolute Shrinkage and Selection Operator method, uses HIV envelope sequence from phenotypically characterized clones. Prediction of R5X4/X4 viruses was 86% sensitive and that of R5 viruses was 89% specific with our model. The overall accuracy of THETA was 88%, making it sufficiently reliable for predicting the tropism of subtype CRF02-AG sequences. Availability and implementation Binaries are freely available for download at https://github.com/viro-tls/THETA. It was implemented in Matlab and supported on MS Windows platform. The sequence data used in this work are available from GenBank under the accession numbers MK618182-MK618417.

Published
2019
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2. Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry

Author

Mathieu Claireaux, Rémy Robinot, Jérôme Kervevan, Mandar Patgaonkar, Isabelle Staropoli, Anne Brelot, Alexandre Nouël, Stacy Gellenoncourt, Xian Tang, Mélanie Héry, Stevenn Volant, Emeline Perthame, Véronique Avettand-Fenoël, Julian Buchrieser, Thomas Cokelaer, Christiane Bouchier, Laurence Ma, Faroudy Boufassa, Samia Hendou, Valentina Libri, Milena Hasan, David Zucman, Pierre de Truchis, Olivier Schwartz, Olivier Lambotte, Lisa A. Chakrabarti, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomics (plateforme technologique), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Hôpital Foch [Suresnes], Hôpital Raymond Poincaré [AP-HP], Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), This work was supported by grants to L.A.C. from ANRS (17218 and 19206), Institut Pasteur (PasteurInnov TETRHIS), and ANR (14 CE 16002901). The Biomics Platform is a member of the 'France Génomique' consortium (ANR10-INBS-09-08). M.C. was the recipient of a Sidaction fellowship, R.R. of a Pasteur Carnot MS and a Sidaction fellowships, M.P. of an ANRS fellowship, and S.G. of a MESR/Université de Paris fellowship., We are grateful to patients who participated in the study. We thank the investigators of the ANRS CO21 CODEX cohort and Camille Lecuroux for help with recruitment of controller patients, Morgane Marcou and Katia Bourdic for help with recruitment of treated patients, Bernard Lagane for the gift of plamids, and Sophie Novault from the Pasteur CB UTechS for advice on cell sorting. MHC class II tetramer reagents were provided by the NIH Tetramer Core facility at Emory University. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 PTE Gag peptide set (Cat # 11554)., ANR-14-CE16-0029,PD1VAX,Une nouvelle stratégie de vaccination par vecteur ADN PD1 pour mimer les réponses spécifiques de Gag trouvées chez les contrôleurs spontanés du VIH(2014), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)

Subjects
CD4-Positive T-Lymphocytes, Viral membrane fusion, MESH: Mutation, Receptors, CXCR3, Receptors, CCR5, Science, MESH: Virus Internalization, viruses, General Physics and Astronomy, Down-Regulation, Gene Products, gag, HIV Infections, MESH: Receptors, CCR5, MESH: Down-Regulation, General Biochemistry, Genetics and Molecular Biology, Article, MESH: Receptors, CXCR3, MESH: HIV-1, MESH: Elite Controllers, Humans, MESH: Humans, Multidisciplinary, Retrovirus, Histocompatibility Antigens Class II, MESH: CD4-Positive T-Lymphocytes, virus diseases, MESH: HIV Infections, General Chemistry, Virus Internalization, MESH: Chemokines, MESH: Gene Expression Regulation, Gene Expression Regulation, MESH: Gene Products, gag, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Mutation, MESH: Histocompatibility Antigens Class II, HIV-1, Chemokines, Elite Controllers
Abstract

HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control., Here, Claireaux et al. show that people who naturally control HIV infection express lower levels of the viral co-receptor CCR5 in specific CD4+ T cells, and that this results from mutations or receptor internalization by CD4+ T cell-produced chemokines.

Published
2019
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3. CXCR6-Mediated Simian Immunodeficiency Virus SIVagmSab Entry into Sabaeus African Green Monkey Lymphocytes Implicates Widespread Use of Non-CCR5 Pathways in Natural Host Infections

Author

Cristian Apetrei, Katherine S. Wetzel, Yanjie Yi, Sarah T. C. Elliott, Beatrice Jacquelin, Beatrice H. Hahn, Dino C. Romero, Ronald G. Collman, Ivona Pandrea, Michaela Müller-Trutwin, University of Pennsylvania [Philadelphia], HIV, Inflammation et persistance, Institut Pasteur [Paris], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), This work was funded by NIH grants R56-AI091516 and R01-MH06119 (R.G.C.), 2T32AI007632 (K.S.W.), R37-AI050529 (B.H.H.), and R01HL117715 (C.A. and I.P.). We also acknowledge assistance from multiple cores of the Penn Center for AIDS Research (P30-AI045008)., We thank F. Bibollet-Ruche, R. Warrier, and G. Learn for valuable advice and S. Bryan and F. Shaheen for technical assistance., University of Pennsylvania, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, MESH: Sequence Analysis, DNA, Lymphocyte, viruses, MESH: Virus Internalization, [SDV]Life Sciences [q-bio], Simian Acquired Immunodeficiency Syndrome, MESH: Receptors, CCR6, MESH: Receptors, CCR5, medicine.disease_cause, 0302 clinical medicine, Viral Envelope Proteins, Chlorocebus aethiops, natural host, MESH: Animals, Lymphocytes, Cloning, Molecular, MESH: Phylogeny, Immunodeficiency, Phylogeny, tropism, virus diseases, MESH: CD4-Positive T-Lymphocytes, coreceptor, 3. Good health, medicine.anatomical_structure, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Receptors, Virus, MESH: Simian Acquired Immunodeficiency Syndrome, Viral load, Receptors, CCR6, simian immunodeficiency virus, Receptors, CCR5, T cell, Immunology, MESH: Simian Immunodeficiency Virus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Microbiology, 03 medical and health sciences, Virology, medicine, Animals, MESH: Cloning, Molecular, Tropism, MESH: Host-Pathogen Interactions, Sequence Analysis, DNA, Simian immunodeficiency virus, Virus Internalization, medicine.disease, MESH: Receptors, Virus, MESH: Cercopithecus aethiops, CXCR6, African green monkey, Viral Tropism, 030104 developmental biology, Viral replication, Insect Science, MESH: Viral Envelope Proteins, Pathogenesis and Immunity, MESH: Lymphocytes, African Green Monkey, MESH: Viral Tropism, 030215 immunology
Abstract

African green monkeys (AGM) and sooty mangabeys (SM) are well-studied natural hosts of simian immunodeficiency virus (SIV) that do not progress to AIDS when infected with their species-specific viruses. Natural hosts of SIV express very low levels of the canonical entry coreceptor CCR5, and recent studies have shown that CCR5 is dispensable for SIV infection of SM in vivo and that blocking of CCR5 does not prevent ex vivo infection of peripheral blood mononuclear cells (PBMC) from SM or vervet AGM. In both hosts, CXCR6 is an efficient entry pathway in vitro . Here we investigated the use of species-matched CXCR6 and other alternative coreceptors by SIVagmSab, which infects sabaeus AGM. We cloned sabaeus CD4 and 10 candidate coreceptors. Species-matched CXCR6, CCR5, and GPR15 mediated robust entry into transfected cells by pseudotypes carrying SIVagmSab92018ivTF Env, with lower-level entry through GPR1 and APJ. We cloned genetically divergent env genes from the plasma of two wild-infected sabaeus AGM and found similar patterns of coreceptor use. Titration experiments showed that CXCR6 and CCR5 were more efficient than other coreceptors when tested at limiting CD4/coreceptor levels. Finally, blocking of CXCR6 with its ligand CXCL16 significantly inhibited SIVagmSab replication in sabaeus PBMC and had a greater impact than did the CCR5 blocker maraviroc, confirming the use of CXCR6 in primary lymphocyte infection. These data suggest a new paradigm for SIV infection of natural host species, whereby a shared outcome of virus-host coevolution is the use of CXCR6 or other alternative coreceptors for entry, which may direct SIV toward CD4 + T cell subsets and anatomical sites that support viral replication without disrupting immune homeostasis and function. IMPORTANCE Natural hosts of SIV do not progress to AIDS, in stark contrast to pathogenic human immunodeficiency virus type 1 (HIV-1)-human and SIVmac-macaque infections. Identifying how natural hosts avoid immunodeficiency can elucidate key mechanisms of pathogenesis. It is known that despite high viral loads, natural hosts have a low frequency of CD4 + cells expressing the SIV coreceptor CCR5. In this study, we demonstrate the efficient use of the coreceptor CXCR6 by SIVagmSab to infect sabaeus African green monkey lymphocytes. In conjunction with studies of SIVsmm, which infects sooty mangabeys, and SIVagmVer, which infects vervet monkeys, our data suggest a unifying model whereby in natural hosts, in which the CCR5 expression level is low, the use of CXCR6 or other coreceptors to mediate infection may target SIV toward distinct cell populations that are able to support high-level viral replication without causing a loss of CD4 + T cell homeostasis and lymphoid tissue damage that lead to AIDS in HIV-1 and SIVmac infections.

Published
2017
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4. Concordance between Two Phenotypic Assays and Ultradeep Pyrosequencing for Determining HIV-1 Tropism

Author

Saliou, Adrien, Delobel, Pierre, Dubois, Martine, Nicot, Florence, Raymond, Stéphanie, Calvez, Vincent, Masquelier, Bernard, Izopet, Jacques, Renseigné, Non, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Service des Maladies Infectieuses et Tropicales, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Virology Laboratory, Hospital, Laboratoire de Virologie, Unité de Mathématiques Pures et Appliquées (UMPA-ENSL), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, VIROLOGIE, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Receptors, CXCR4, MESH: Sequence Analysis, DNA, Concordance, Viral quasispecies, MESH: Receptors, CCR5, Biology, MESH: Phenotype, Antiviral Agents, MESH: Receptors, CXCR4, MESH: HIV-1, 03 medical and health sciences, Genotype, Humans, Pharmacology (medical), Genotyping, Tropism, 030304 developmental biology, Pharmacology, Genetics, 0303 health sciences, MESH: Humans, MESH: Middle Aged, 030306 microbiology, virus diseases, MESH: Adult, Sequence Analysis, DNA, Middle Aged, Virology, 3. Good health, Viral Tropism, Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, CCR5 Receptor Antagonists, HIV-1, Tissue tropism, Pyrosequencing, MESH: Viral Tropism, Trofile assay
Abstract

There have been few studies on the concordance between phenotypic assays for predicting human immunodeficiency virus type 1 (HIV-1) coreceptor usage. The sensitivity of ultradeep pyrosequencing combined with genotyping tools is similar to that of phenotypic assays for detecting minor CXCR4-using variants. We evaluated the agreement between two phenotypic assays, the Toulouse tropism test (TTT) and the Trofile assay, and ultradeep pyrosequencing for determining the tropism of HIV-1 quasispecies. The concordance between the TTT and Trofile assays was assessed for 181 samples successfully phenotyped by both assays. The TTT was 86% concordant with the standard Trofile assay and 91.7% with its enhanced-sensitivity version. The concordance between phenotypic characterization of HIV-1 tropism and ultradeep pyrosequencing genotypic prediction was further studied in selected samples. The HIV-1 tropism inferred from ultradeep pyrosequencing of 11 samples phenotyped as X4 and dualtropic and 12 phenotyped as R5-tropic agreed closely with the results of phenotyping. However, ultradeep pyrosequencing detected minor CXCR4-using variants in 3 of 12 samples phenotyped as R5-tropic. Ultradeep pyrosequencing also detected minor CXCR4-using variants that had been missed by direct sequencing in 6 of 9 samples phenotyped as X4-tropic but genotyped as R5-tropic by direct sequencing. Ultradeep pyrosequencing was 87% concordant with the Trofile and TTT phenotypic assays and was in the same range of sensitivity (0.4%) than these two phenotypic assays (0.3 to 0.5%) for detecting minor CXCR4-using variants. Ultradeep pyrosequencing provides a new way to improve the performance of genotypic prediction of HIV-1 tropism to match that of the phenotypic assays.

Published
2011
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5. Evaluation of the Genotypic Prediction of HIV-1 Coreceptor Use versus a Phenotypic Assay and Correlation with the Virological Response to Maraviroc: the ANRS GenoTropism Study

Author

Recordon-Pinson, Patricia, Soulié, Cathia, Flandre, Philippe, Descamps, Diane, Lazrek, Mouna, Charpentier, Charlotte, Montes, Brigitte, Trabaud, Mary-Anne, Cottalorda, Jacqueline, Schneider, Véronique, Morand-Joubert, Laurence, Tamalet, Catherine, Desbois, Delphine, Macé, Muriel, Ferré, Virginie, Vabret, Astrid, Ruffault, Annick, Pallier, Coralie, Raymond, Stéphanie, Izopet, Jacques, Reynes, Jacques, Marcelin, Anne-Geneviève, Masquelier, Bernard, Renseigné, Non, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Virology Laboratory, Hôpital Rothchild, Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Virology, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Human and Molecular Virology, Georges Clémenceau Universitary Hospital, Unité de Rétrovirologie, Hôpital Pontchaillou, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire de Virologie, Institut Fédératif de Biologie de Purpan, Variabilité génomique des virus, Université Bordeaux Segalen - Bordeaux 2-IFR66, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Microbiologie Fondamentale et Pathogénicité (MFP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Oncology, MESH: Sequence Analysis, DNA, Multivariate analysis, HIV Infections, HIV Envelope Protein gp120, MESH: Receptors, CCR5, Maraviroc, MESH: Genotype, MESH: HIV-1, Correlation, MESH: HIV Envelope Protein gp120, chemistry.chemical_compound, HIV Protease, HIV Fusion Inhibitors, Genotype, MESH: Receptors, HIV, Pharmacology (medical), MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, MESH: Tropism, MESH: HIV Infections, Middle Aged, MESH: Cyclohexanes, HIV Reverse Transcriptase, 3. Good health, Phenotype, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, CCR5 Receptor Antagonists, Lentivirus, Female, Viral load, Adult, medicine.medical_specialty, Receptors, CCR5, MESH: HIV Reverse Transcriptase, Molecular Sequence Data, CCR5 receptor antagonist, Biology, MESH: Phenotype, Antiviral Agents, Sensitivity and Specificity, Tropism, MESH: HIV Protease, 03 medical and health sciences, Receptors, HIV, Cyclohexanes, Internal medicine, medicine, Humans, MESH: HIV Fusion Inhibitors, 030304 developmental biology, Pharmacology, MESH: Humans, MESH: Molecular Sequence Data, 030306 microbiology, MESH: Adult, Sequence Analysis, DNA, Triazoles, biology.organism_classification, Virology, MESH: Male, MESH: Sensitivity and Specificity, MESH: Triazoles, chemistry, Expanded access, HIV-1, MESH: Female
Abstract

Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of

Published
2010
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6. CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface

Author

Georges Bismuth, Mark G.H. Scott, Catherine Labbé-Jullié, Lamia Achour, Hamasseh Shirvani, Stefano Marullo, Alain Thuret, Marullo, Stefano, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH : Hela Cells, Chemokine receptor CCR5, viruses, Receptor expression, MESH: Antigens, CD4, Intracellular Space, MESH : Intracellular Space, MESH: Cricetinae, Plasma protein binding, MESH: Receptors, CCR5, Endoplasmic Reticulum, Biochemistry, MESH: Cell Compartmentation, MESH : Protein Transport, MESH: Cricetulus, Cell–cell interaction, Cricetinae, MESH : CHO Cells, MESH: Animals, Receptor, Cells, Cultured, MESH : Endoplasmic Reticulum, biology, MESH : Cricetinae, virus diseases, MESH : Protein Binding, MESH : Receptors, CCR5, Hematology, Cell biology, Protein Transport, Antigens, Surface, CD4 Antigens, MESH: Intracellular Space, MESH : Antigens, Surface, Intracellular, MESH: Cells, Cultured, Protein Binding, MESH: Protein Transport, Receptors, CCR5, MESH: Antigens, Surface, MESH : Cricetulus, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, CHO Cells, Article, Cricetulus, MESH: CHO Cells, MESH: Endoplasmic Reticulum, MESH : Cells, Cultured, MESH: Protein Binding, Animals, Humans, MESH : Cell Compartmentation, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Humans, Endoplasmic reticulum, MESH : Humans, Cell Biology, Cell Compartmentation, MESH: Hela Cells, biology.protein, MESH : Antigens, CD4, MESH : Animals, CC chemokine receptors, HeLa Cells
Abstract

International audience; The association of CD4, a glycoprotein involved in T-cell development and antigen recognition, and CC chemokine receptor 5 (CCR5), a chemotactic G protein-coupled receptor, which regulates trafficking and effector functions of immune cells, forms the main receptor for HIV. We observed that the majority of CCR5 is maintained within the intracellular compartments of primary T lymphocytes and in a monocytic cell line, contrasting with its relatively low density at the cell surface. The CCR5-CD4 association, which occurs in the endoplasmic reticulum, enhanced CCR5 export to the plasma membrane in a concentration-dependent manner, whereas inhibition of endogenous CD4 with small interfering RNAs decreased cell-surface expression of endogenous CCR5. This effect was specific for CCR5, as CD4 did not affect cellular distribution of CXCR4, the other HIV coreceptor. These results reveal a previously unappreciated role of CD4, which contributes to regulating CCR5 export to the plasma membrane.

Published
2009
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7. Genomic studies in AIDS: problems and answers. Development of a statistical model integrating both longitudinal cohort studies and transversal observations of extreme cases

Author

Colette Huber, Jean-François Zagury, Laurent Jacquemin, Houria Hendel, Odile Pons, Philippe Haumont, Sara Tamim, Kaniewski, Nadine, Epidémiologie et Biostatistique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de biométrie et intelligence artificielle de Jouy (MIA-JOUY), Institut National de la Recherche Agronomique (INRA), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biométrie, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Recherche Agronomique ( INRA ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Candidate gene, MESH : Polymorphism, Genetic, Cross-sectional study, HIV Infections, MESH : Models, Biological, MESH: Receptors, CCR5, MESH: NAD(P)H Dehydrogenase (Quinone), Cohort Studies, MESH : HLA Antigens, HLA Antigens, Models, Receptors, NAD(P)H Dehydrogenase (Quinone), MESH : NAD(P)H Dehydrogenase (Quinone), Longitudinal Studies, MESH: Longitudinal Studies, MESH: Cohort Studies, MESH: HLA Antigens, MESH : Longitudinal Studies, Genetics, education.field_of_study, MESH : Acquired Immunodeficiency Syndrome, MESH : Models, Statistical, MESH : Receptors, CCR5, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: HIV Infections, General Medicine, Statistical, No, Cohort, MESH : Research Support, No, Cohort study, Receptors, CCR5, Population, MESH : Cohort Studies, Human leukocyte antigen, Biology, Research Support, Models, Biological, Genetic determinism, Genetic, MESH: Polymorphism, Genetic, MESH : HIV Infections, Humans, Polymorphism, education, Alleles, MESH: Acquired Immunodeficiency Syndrome, Pharmacology, Acquired Immunodeficiency Syndrome, Models, Statistical, Polymorphism, Genetic, MESH: Humans, MESH: Alleles, MESH : Humans, Haplotype, MESH: Models, Biological, Biological, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Research Support, No, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Alleles, CCR5, MESH: Models, Statistical, Demography
Abstract

Genomic studies developed to understand HIV-1 infection and pathogenesis have often lead to conflicting results. This is linked to various factors, including differences in cohort design and selection, the numbers of patients involved, the influence of population substructure, the ethnic origins of the participants, and phenotypic definition. These difficulties in the interpretation of results are examined through published studies on the role of polymorphisms in HLA and the chemokine receptors genes in AIDS. Our analysis suggests that the use of haplotypes will strengthen the results obtained in a given cohort, and meta-analysis including multiple cohorts to gather large-enough numbers of patients should also allow clarification of the genetic associations observed. A P-value of 0.001 appears to be a good compromise for significance on candidate genes in a genetic study. Due to the generally limited size of available cohorts, results will have to be validated in other cohorts. We developed a model to fit transversal case studies (extreme case-control studies) with longitudinal cohorts (all-stages patients) for observations on two gene polymorphisms of CCR5 and NQO1. Interestingly, we observe a protective effect for the CCR5-D32 mutant allele in 95% of the simulations based on that model when using a population of 600 subjects; however, when using populations of 250 subjects we find a significant protection in only 59% of the simulations. Our model gives thus an explanation for the discrepancies observed in the various genomic studies published in AIDS on CCR5-D32 and other gene polymorphisms: they result from statistical fluctuations due to a lack of power. The sizes of most seroconverter cohorts presently available seem thus insufficient since they include less than a few hundred subjects. This result underlines the power and usefulness of the transversal studies involving extreme patients and their complementarity to longitudinal studies involving seroconverter cohorts. The transposition approach of extreme case-control data into longitudinal analysis should prove useful not only in AIDS but also in other diseases induced by chronic exposure to a foreign agent or with chronic clinical manifestations. © 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

Published
2003
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8. Isolated human astrocytes are not susceptible to infection by M- and T-tropic HIV-1 strains despite functional expression of the chemokine receptors CCR5 and CXCR4

Author

Pierre-Marie Lledo, Jean-Didier Vincent, Agnès Boutet, Jean-François Delfraissy, Yassine Taoufik, Hassan Salim, Marc Tardieu, La réponse immunitaire anti-VIH systémique et cérébrale : aspects physiopathologiques et thérapeutiques, Institut National de la Santé et de la Recherche Médicale (INSERM), Développement, évolution et plasticité du système nerveux (DEPSN), Centre National de la Recherche Scientifique (CNRS), and Institut de Neurobiologie Alfred Fessard (INAF)

Subjects
Eotaxin, Chemokine, AIDS Dementia Complex, T-Lymphocytes, MESH: Antigens, CD4, MESH: Neurons, chemokine receptors, MESH: Receptors, CCR5, MESH: HIV-1, Chemokine receptor, 0302 clinical medicine, MESH: RANTES, Chemokine CCL4, Chemokine CCL5, Cells, Cultured, Neurons, 0303 health sciences, biology, Microglia, Brain, virus diseases, Macrophage Inflammatory Proteins, Immunohistochemistry, 3. Good health, MESH: Microglia, medicine.anatomical_structure, MESH: Macrophage Inflammatory Protein-1, Neurology, MESH: Calcium, CD4 Antigens, Neuroglia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Receptors, Chemokine, Chemokines, CXC, MESH: Cells, Cultured, Astrocyte, Receptors, CXCR4, Receptors, CCR5, Receptors, CCR3, MESH: Calcium Signaling, MESH: Receptors, CXCR4, MESH: Coculture Techniques, MESH: Brain, 03 medical and health sciences, Cellular and Molecular Neuroscience, Fetus, microglial cells, Viral entry, MESH: AIDS Dementia Complex, medicine, Humans, Calcium Signaling, RNA, Messenger, development, MESH: Chemokines, CXC, MESH: RNA, Messenger, 030304 developmental biology, MESH: Humans, Macrophages, HIV, MESH: Macrophages, MESH: Immunohistochemistry, MESH: Fetus, Molecular biology, CD4, Chemokine CXCL12, Coculture Techniques, MESH: Astrocytes, MESH: T-Lymphocytes, Cell culture, Astrocytes, HIV-1, biology.protein, Calcium, MESH: Receptors, Chemokine, 030217 neurology & neurosurgery
Abstract

Within the brain, HIV-1 targets the microglia and astrocytes. Previous studies have reported that viral entry into astrocytes is independent of CD4, in contrast to microglia. We aimed to determine whether chemokine receptors play a role in mediating CD4-independent HIV-1 entry into astrocytes. We found that embryonic astrocytes and microglial cells express CCR5, CCR3, and CXCR4 transcripts. Intracellular calcium levels in astrocytes were found to increase following application of RANTES, MIP-1beta (CCR5-agonist), SDF-1alpha (CXCR4-agonist), but not eotaxin (CCR3-agonist). In microglial cells, eotaxin was also able to modulate internal calcium homeostasis. CD4 was not present at the cell surface of purified astrocytes but CD4 mRNA could be detected by RT-PCR. Neither HIV-1(9533) (R5 isolate) nor HIV-1(LAI) (X4 isolate) penetrated into purified astrocytes. In contrast, mixed CNS cell cultures were infected by HIV-1(9533) and this was inhibited by anti-CD4 mAb in 4/4 tested cultures and by anti-CCR5 mAb in 2/4. Thus, the HIV-1 R5 strain requires CD4 to penetrate into brain cells, suggesting that CCR5 cannot be used as the primary receptor for M-tropic HIV-1 strains in astrocytes. Moreover, inconstant inhibition of HIV-1 entry by anti-CCR5 mAb supports the existence of alternative coreceptors for penetration of M-tropic isolates into brain cells.

Published
2001
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9. HIV-1 dynamics and coreceptor usage in Maraviroc-treated patients with ongoing replication

Author

P, Recordon-Pinson, S, Raymond, P, Bellecave, A G, Marcelin, C, Soulie, D, Descamps, V, Calvez, P R, Harrigan, H, Fleury, J, Izopet, B, Masquelier, Theresa, Mo, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Numerical Medicine (NUMED), Unité de Mathématiques Pures et Appliquées (UMPA-ENSL), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), British Columbia Centre for Excellence in HIV/AIDS [Vancouver], Laboratoire de Virologie, BC Centre for Excellence in HIV/AIDS, ANRS AC11 Resistance Study Group, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Laboratoire de Virologie [Purpan], CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Unité de Mathématiques Pures et Appliquées (UMPA-ENSL), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon), and Le Corre, Morgane

Subjects
MESH: Selection, Genetic, HIV Infections, HIV Envelope Protein gp120, V3 loop, MESH: Receptors, CCR5, Maraviroc, MESH: Genotype, MESH: HIV-1, chemistry.chemical_compound, MESH: HIV Envelope Protein gp120, HIV Fusion Inhibitors, Genotype, MESH: Sequence Analysis, RNA, Pharmacology (medical), MESH: Peptide Fragments, MESH: High-Throughput Nucleotide Sequencing, MESH: Evolution, Molecular, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, 0303 health sciences, education.field_of_study, MESH: Drug Resistance, Viral, High-Throughput Nucleotide Sequencing, virus diseases, MESH: HIV Infections, MESH: Cyclohexanes, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Viral evolution, CCR5 Receptor Antagonists, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Receptors, CXCR4, Receptors, CCR5, Population, Viral quasispecies, Biology, Antiviral Agents, MESH: Receptors, CXCR4, Evolution, Molecular, 03 medical and health sciences, Cyclohexanes, Drug Resistance, Viral, Humans, Selection, Genetic, education, MESH: HIV Fusion Inhibitors, Tropism, 030304 developmental biology, Pharmacology, MESH: Humans, Sequence Analysis, RNA, 030306 microbiology, Triazoles, Virology, Peptide Fragments, body regions, Viral Tropism, chemistry, MESH: Triazoles, HIV-1, Tissue tropism, MESH: Viral Tropism, human activities
Abstract

There is evidence that HIV-1 evolution under maraviroc (MVC) pressure can lead to the selection of either X4-tropic variants and/or R5-tropic, MVC-resistant isolates. However, the viral dynamics of HIV-1 variants in patients with virological failure (VF) on MVC-containing regimens remain poorly studied. Here, we investigated the V3 loop evolution of HIV-1 on MVC in relation to coreceptor usage and the nature of HIV-1 quasispecies before MVC therapy using bulk population sequences and ultradeep sequencing. The majority of patients had no detectable minority X4 variant at baseline. The evolution of tropism was followed up until VF and showed three possibilities for viral evolution in these patients: emergence of preexisting X4 variants, de novo selection of R5 variants presenting V3 loop mutations, or replication of R5 variants without selection of known mutations.

Published
2013
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10. In vitro effect of anti-human immunodeficiency virus CCR5 antagonist maraviroc on chemotactic activity of monocytes, macrophages and dendritic cells

Author

Claudio Maria Mastroianni, Raffaella Rossi, Fabio Mengoni, Miriam Lichtner, Ilaria Sauzullo, Vincenzo Vullo, Anna Paola Massetti, A. De Rosa, Department of Public Health and Infectious Diseases, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Università degli Studi di Roma 'La Sapienza' [Rome] - Réseau International des Instituts Pasteur - Institut Pasteur - Fondation Cenci Bolognetti

Subjects
MESH: Chemotaxis, Chemokine, Translational Studies, Chemokine receptor CCR5, MESH: Chemotaxis, Leukocyte, HIV Infections, MESH: Receptors, CCR5, MESH: Monocytes, Monocytes, Maraviroc, 0302 clinical medicine, HIV Fusion Inhibitors, Immunology and Allergy, 030212 general & internal medicine, Chemokine CCL4, Chemokine CCL5, Chemokine CCL2, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, MESH: Dendritic Cells, MESH: N-Formylmethionine Leucyl-Phenylalanine, biology, Chemotaxis, MESH: HIV Infections, MESH: Cyclohexanes, 3. Good health, N-Formylmethionine Leucyl-Phenylalanine, Chemotaxis, Leukocyte, medicine.anatomical_structure, CCR5 Receptor Antagonists, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ccr5, hiv, maraviroc, dendritic cells, chemotaxis, Receptors, CCR5, [SDV.IMM] Life Sciences [q-bio]/Immunology, CD14, Immunology, CCR5 receptor antagonist, CCL2, 03 medical and health sciences, Cyclohexanes, medicine, Humans, MESH: Chemokine CCL5, MESH: Chemokine CCL4, MESH: HIV Fusion Inhibitors, MESH: Chemokine CCL2, 030304 developmental biology, MESH: Humans, Formyl peptide receptor, Macrophages, Monocyte, MESH: Macrophages, Dendritic Cells, Triazoles, MESH: Triazoles, biology.protein
Abstract

Summary Compounds targeting the chemokine receptor CCR5 have recently been approved for treatment of human immunodeficiency virus (HIV) infection. Given the central role of CCR5 in inflammation and recruitment of antigen-presenting cells (APC), it is important to investigate the immunological consequences of pharmacological inhibition of CCR5. We evaluated the in vitro effect of different concentrations of CCR5 antagonist maraviroc (MVC) on cell migration of monocytes, macrophages (MO) and monocyte-derived dendritic cells (MDC) towards peptide formyl-methionyl-leucyl-phenylalanine (fMLP) and chemokines regulated upon activation normal T cell expressed and secreted (RANTES) and CCL4/macrophage inflammatory protein-1 (MIP-1β) and CCL2/monocyte chemotactic protein-1 (MCP-1). Results of flow cytometric analysis showed that monocytes treated in vitro with MVC exhibited a significant dose-dependent reduction of chemotaxis towards MIP-1β and MCP-1. fMLP-induced chemotactic activity decreased only at higher concentration (1 µM and 10 µM of MVC). In addition, all concentrations of MVC (0·1, 1 and 10 µM) induced in vitro a significant inhibition of chemotaxis of MO and MDC in response to all tested chemoattractants. No change in phenotype (CD1a and CD14) and CCR1, CCR4, CCR5 and formyl peptide receptor (FPR) expression was seen after in vitro treatment with MVC. These findings suggest that CCR5 antagonist MVC may have the in vitro ability of inhibiting the migration of innate immune cells by mechanism which could be independent from the pure anti-HIV effect. The drug might have a potential role in the down-regulation of HIV-associated chronic inflammation by blocking the recirculation and trafficking of MO and MDC.

Published
2011
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11. Is long-term virological response related to CCR5 Delta32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?: CCR5 D32 in HIV treated patients

Author

J-J, Laurichesse, A, Taieb, C, Capoulade-Metay, C, Katlama, V, Villes, M-C, Drobacheff-Thiebaud, F, Raffi, G, Chêne, I, Theodorou, C, Leport, J M, Besnier, Laboratoire de recherche en pathologie infectieuse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie cellulaire et tissulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie et Sciences Sociales Appliquées à l'Innovation Médicale, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), ANRS C08 Aproco-Copilote study group, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, MESH: CD4 Lymphocyte Count, HIV Infections, MESH: Logistic Models, 030312 virology, MESH: Receptors, CCR5, Gastroenterology, Polymerase Chain Reaction, MESH: Antiretroviral Therapy, Highly Active, Virological response, MESH: HIV-1, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Medicine, HIV Protease Inhibitor, Pharmacology (medical), CCR5 D32 deletion, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Sida, MESH: Treatment Outcome, 0303 health sciences, biology, Health Policy, Confounding, Age Factors, MESH: HIV Infections, 3. Good health, Infectious Diseases, Treatment Outcome, MESH: RNA, Viral, Cohort, RNA, Viral, Female, Viral load, Cart, Adult, medicine.medical_specialty, Receptors, CCR5, antiretroviral therapy, virological response, Article, MESH: Multivariate Analysis, 03 medical and health sciences, Internal medicine, Humans, Alleles, MESH: HIV Protease Inhibitors, MESH: Age Factors, MESH: Humans, business.industry, MESH: Alleles, HIV, MESH: Adult, MESH: Polymerase Chain Reaction, HIV Protease Inhibitors, biology.organism_classification, MESH: Male, MESH: Prospective Studies, CD4 Lymphocyte Count, Logistic Models, MESH: Gene Deletion, Immunology, Multivariate Analysis, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Gene Deletion
Abstract

International audience; OBJECTIVE: The aim of the study was to determine whether the chemokine (C-C motif) receptor 5 (CCR5) Delta32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1-infected patients. METHODS: The genetic substudy of the Agence Nationale de Recherche sur le SIDA (ANRS) CO8 APROCO-COPILOTE cohort included 609 patients who started protease inhibitor-containing cART in 1997-1999. Patients were considered to have a sustained virological response if all plasma HIV RNA measurements in the period considered were

Published
2010
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12. Is long-term virological response related to CCR5 Delta32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?

Author

Laurichesse, Jean-Jacques, Taieb, Audrey, Capoulade-Metay, Corinne, Katlama, Christine, Villes, Virginie, Drobacheff-Thiebaud, Marie-Christine, Raffi, François, Chêne, Genevieve, Theodorou, Ioannis, Leport, Catherine, Laboratoire de recherche en pathologie infectieuse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie cellulaire et tissulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie et Sciences Sociales Appliquées à l'Innovation Médicale, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), ANRS C08 Aproco-Copilote study group, and Mouillet, Evelyne

Subjects
MESH: Age Factors, MESH: Humans, MESH: CD4 Lymphocyte Count, MESH: Alleles, antiretroviral therapy, virological response, HIV, MESH: Adult, MESH: Logistic Models, MESH: Polymerase Chain Reaction, MESH: HIV Infections, MESH: Receptors, CCR5, MESH: Male, MESH: Multivariate Analysis, MESH: Prospective Studies, MESH: Antiretroviral Therapy, Highly Active, MESH: HIV-1, MESH: Gene Deletion, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: RNA, Viral, CCR5 D32 deletion, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, MESH: Treatment Outcome, MESH: HIV Protease Inhibitors
Abstract

International audience; OBJECTIVE: The aim of the study was to determine whether the chemokine (C-C motif) receptor 5 (CCR5) Delta32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1-infected patients. METHODS: The genetic substudy of the Agence Nationale de Recherche sur le SIDA (ANRS) CO8 APROCO-COPILOTE cohort included 609 patients who started protease inhibitor-containing cART in 1997-1999. Patients were considered to have a sustained virological response if all plasma HIV RNA measurements in the period considered were

Published
2010
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13. Identification of nonpeptide CCR5 receptor agonists by structure-based virtual screening

Author

Jean-Yves Springael, Didier Rognan, Marc Parmentier, Jean-Luc Galzi, Esther Kellenberger, Muriel Hachet-Haas, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Faculteit Toegepaste Economische Wetenschappen (TEW), University of Antwerp (UA), Agence Universitaire de la Francophonie (AUF), Récepteurs et protéines membranaires (RPM), Centre National de la Recherche Scientifique (CNRS), Pharmacochimie de la communication cellulaire (PCC), Instiitut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université de Bruxelles, Université libre de Bruxelles (ULB), Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)

Subjects
Models, Molecular, Pyrrolidines, Chemokine receptor CCR5, MESH: Sequence Homology, Amino Acid, MESH: Piperazines, Quantitative Structure-Activity Relationship, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Amino Acid Sequence, MESH: Receptors, CCR5, 01 natural sciences, Piperazines, MESH: Protein Structure, Tertiary, Piperidines, Drug Discovery, Receptor, 0303 health sciences, MESH: Quantitative Structure-Activity Relationship, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Molecular Structure, Chemistry, virus diseases, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Pyridazines, MESH: Quinazolines, MESH: Piperidines, CCR5 Receptor Antagonists, Molecular Medicine, Pharmacophore, [CHIM.CHEM]Chemical Sciences/Cheminformatics, MESH: Models, Molecular, Agonist, Receptors, CCR5, Stereochemistry, medicine.drug_class, In silico, MESH: Molecular Structure, Molecular Sequence Data, CCR5 receptor antagonist, Computational biology, 03 medical and health sciences, MESH: Pyridazines, medicine, Amino Acid Sequence, 030304 developmental biology, Virtual screening, MESH: Molecular Sequence Data, MESH: Pyrrolidines, Sequence Homology, Amino Acid, Triazoles, 0104 chemical sciences, Protein Structure, Tertiary, 010404 medicinal & biomolecular chemistry, MESH: Triazoles, Docking (molecular), biology.protein, Quinazolines
Abstract

International audience; A three-dimensional model of the chemokine receptor CCR5 has been built to fulfill structural peculiarities of its alpha-helix bundle and to distinguish known CCR5 antagonists from randomly chosen drug-like decoys. In silico screening of a library of 1.6 million commercially available compounds against the CCR5 model by sequential filters (drug-likeness, 2-D pharmacophore, 3-D docking, scaffold clustering) yielded a hit list of 59 compounds, out of which 10 exhibited a detectable binding affinity to the CCR5 receptor. Unexpectedly, most binders tested in a functional assay were shown to be agonists of the CCR5 receptor. A follow-up database query based on similarity to the most potent binders identified three new CCR5 agonists. Despite a moderate affinity of all nonpeptide ligands for the CCR5 receptor, one of the agonists was shown to promote efficient receptor internalization, which is a process therapeutically favorable for protection against HIV-1 infection.

Published
2007
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14. Polymorphisms in chemokine and chemokine receptor genes and the development of coal workers' pneumoconiosis

Author

Selma Rivas-Fuentes, Christophe Combadière, Rachel Nadif, Steven R. Kleeberger, Margaret Mintz, Anne E. Jedlicka, Mathieu P Rodero, Elise Lavergne, Francine Kauffmann, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie cellulaire et tissulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Biostatistique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Laboratory of Respiratory Biology, National Institutes of Health [Bethesda] (NIH), Action Thématique Concertée Environnement&Santé 2003 ATC-ASE04080LSA, Nadif, Rachel, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
CCR2, Chemokine, [SDV]Life Sciences [q-bio], MESH: Receptors, CCR5, Biochemistry, Gastroenterology, MESH: Genotype, Chemokine receptor, 0302 clinical medicine, Gene Frequency, CX3CR1, Prevalence, Immunology and Allergy, Receptor, Chemokine CCL5, Chemokine CCL2, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Middle Aged, biology, Pneumoconiosis, MESH: Polymorphism, Single Nucleotide, Hematology, Middle Aged, MESH: Chemokines, 3. Good health, MESH: Chemokines, CC, Phenotype, medicine.anatomical_structure, Chemokines, CC, Receptors, Chemokine, MESH: Membrane Proteins, Chemokines, Adult, medicine.medical_specialty, Genotype, Receptors, CCR5, Receptors, CCR2, MESH: Pneumoconiosis, MESH: Receptors, Ch, Immunology, CX3C Chemokine Receptor 1, MESH: Phenotype, Polymorphism, Single Nucleotide, Article, CCL5, 03 medical and health sciences, Internal medicine, MESH: Polymorphism, Genetic, medicine, MESH: Gene Frequency, Humans, MESH: Coal Mining, Molecular Biology, MESH: Chemokine CCL2, MESH: Prevalence, 030304 developmental biology, Polymorphism, Genetic, Lung, MESH: Humans, Membrane Proteins, MESH: Adult, medicine.disease, Coal Mining, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

Chemokines and their receptors are key regulators of inflammation and may participate in the lung fibrotic process. Associations of polymorphisms in CCL5 (G-403A) and its receptor CCR5 (Delta32), CCL2 (A-2578G) and CCR2 (V64I), and CX3CR1 V249I and T280M with coal worker's pneumoconiosis (CWP) were investigated in 209 miners examined in 1990, 1994 and 1999. Coal dust exposure was assessed by job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-year change in CT score, and CWP prevalence in 1999. CCR5 Delta32 carriers had significantly higher CT score in 1990 and 1994 (2.15 vs. 1.28, p=0.01; 3.04 vs. 1.80, p=0.04). The CX3CR1 I249 allele was significantly associated with lower 1990 CT score and lower progression in 4-year change in CT score in CCR5 Delta32 carriers only (p for interaction=0.03 and 0.02). CX3CR1 V249I was associated with lower 1999 CWP prevalence (16.7%, 13.2%, 0.0% for VV, VI and II); the effect was most evident in miners with high dust exposure (31.6%, 21.7%, 0.0%). Our findings indicate that chemokine receptors CCR5 and CX3CR1 may be involved in the development of pneumoconiosis.

Published
2006
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15. The antimicrobial peptide dermaseptin S4 inhibits HIV-1 infectivity in vitro

Author

Laurent Bélec, Héla Saïdi, Frédéric Tangy, Afifa Belaid, Khaled Hani, Françoise Baleux, Clarisse Lorin, Hakim Hocini, Amira Zairi, Virus Lents, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunopathologie humaine, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biochimie, Faculté de médecine de Sousse [Ibn EL Jazzar], Chimie Organique, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
T-Lymphocytes, HIV Infections, Peptide, Herpes simplex virus type 1, MESH: Receptors, CCR5, medicine.disease_cause, MESH: Monocytes, Monocytes, MESH: HIV-1, MESH: Amphibian Proteins, MESH: Animals, Cytotoxicity, Dermaseptin S4, Cells, Cultured, Infectivity, chemistry.chemical_classification, 0303 health sciences, MESH: Microbial Sensitivity Tests, MESH: Dendritic Cells, 030302 biochemistry & molecular biology, MESH: Antimicrobial Cationic Peptides, MESH: HIV Infections, Antimicrobial, 3. Good health, Transcytosis, MESH: Epithelial Cells, MESH: Virion, MESH: Cells, Cultured, Receptors, CCR5, Microbial Sensitivity Tests, Biology, Amphibian Proteins, Cell Line, Microbiology, 03 medical and health sciences, Virology, medicine, Animals, Humans, 030304 developmental biology, Dermaseptin, MESH: Humans, Virion, Epithelial Cells, Dendritic Cells, In vitro, MESH: Cell Line, Herpes simplex virus, MESH: T-Lymphocytes, chemistry, HIV-1, Antimicrobial Cationic Peptides
Abstract

International audience; Most of HIV-1 infections are acquired through sexual contact. In the absence of a preventive vaccine, the development of topical microbicides that can block infection at the mucosal tissues is needed. Dermaseptin S4 (DS4) is an antimicrobial peptide derived from amphibian skin, which displays a broad spectrum of activity against bacteria, yeast, filamentous fungi, and herpes simplex virus type 1. We show here that DS4 inhibits cell-free and cell-associated HIV-1 infection of P4-CCR5 indicator cells and human primary T lymphocytes. The peptide is effective against R5 and X4 primary isolates and laboratory-adapted strains of HIV-1. Its activity is directed against HIV-1 particles by disrupting the virion integrity. Increasing the number of DS4-positive charges reduced cytotoxicity without affecting the antiviral activity. The modified DS4 inhibited HIV-1 capture by dendritic cells and subsequent transmission to CD4(+) T cells, as well as HIV-1 binding on HEC-1 endometrial cells and transcytosis through a tight epithelial monolayer.

Published
2005
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16. Predictive value of anti-cell and anti-human immunodeficiency virus (HIV) humoral responses in HIV-1-exposed seronegative cohorts of European and Asian origin

Author

Giliola Calori, Gianfranco Pancino, Marie Nguyen, Daniela Breda, Janin Nouhin, Samuele E. Burastero, Mario Clerici, Lucia Lopalco, Adriano Lazzarin, Claudia Barassi, L. X. Truong, D. Brunelli, Clara Paolucci, T. T. Luong, Department of immunology and Infectious Deseases, San Raffaele Scientific Institute, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur d'Ho Chi Minh Ville, Department of Immunology, University of Milan, Biologie des Rétrovirus, Institut Pasteur [Paris], Università degli Studi di Milano = University of Milan (UNIMI), and Institut Pasteur [Paris] (IP)

Subjects
CD4-Positive T-Lymphocytes, Male, MESH: HIV Envelope Protein gp41, MESH: Antigens, CD4, MESH: Receptors, CCR5, HIV Antibodies, HIV Envelope Protein gp120, Immunoglobulin G, MESH: HIV-1, Cohort Studies, MESH: HIV Envelope Protein gp120, 0302 clinical medicine, Antibody Specificity, Immunopathology, Odds Ratio, MESH: Cohort Studies, HIV Seronegativity, MESH: HIV Seronegativity, MESH: Immunoglobulin G, 0303 health sciences, MESH: Middle Aged, MESH: Asian Continental Ancestry Group, biology, virus diseases, MESH: CD4-Positive T-Lymphocytes, Environmental exposure, MESH: European Continental Ancestry Group, Middle Aged, HIV Envelope Protein gp41, 3. Good health, CD4 Antigens, Female, Antibody, Adult, Adolescent, Receptors, CCR5, White People, 03 medical and health sciences, Immune system, Asian People, Immunity, Virology, Humans, MESH: Immunoglobulin A, MESH: Antibody Specificity, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: HIV Antibodies, MESH: Adult, MESH: Male, MESH: Odds Ratio, Immunoglobulin A, Immunology, Humoral immunity, biology.protein, HIV-1, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract

Unconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus–cell interactions, IgG to CD4–gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4–gp120 complex) were extremely significant predictors of HIV exposure (P

Published
2005
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17. CCR5 delta32 deletion and response to highly active antiretroviral therapy in HIV-1-infected patients

Author

Guérin, Sylvie, Meyer, Laurence, Theodorou, Ioannis, Boufassa, Faroudy, Magierowska, Magda, Goujard, Cécile, Rouzioux, Christine, Debré, Patrice, Delfraissy, Jean-François, Study Group, The Seroco/hemoco, Epidémiologie, Démographie et Sciences Sociales: santé reproductive, sexualité et infection à VIH (Inserm U569), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d'études démographiques (INED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Santé publique, épidémiologie. Reproduction humaine, Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie cellulaire et tissulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne et maladies infectieuses, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Genotype, Receptors, CCR5, Anti-HIV Agents, medicine.medical_treatment, Immunology, Human immunodeficiency virus (HIV), MESH: Logistic Models, HIV Infections, Biology, MESH: Receptors, CCR5, medicine.disease_cause, MESH: Antiretroviral Therapy, Highly Active, MESH: Genotype, Cohort Studies, Pharmacotherapy, Acquired immunodeficiency syndrome (AIDS), Immunopathology, Antiretroviral Therapy, Highly Active, medicine, Odds Ratio, Immunology and Allergy, Humans, MESH: Anti-HIV Agents, Sida, MESH: Cohort Studies, MESH: Treatment Outcome, Sequence Deletion, Chemotherapy, MESH: Humans, MESH: Follow-Up Studies, MESH: HIV Infections, MESH: Sequence Deletion, medicine.disease, biology.organism_classification, Antiretroviral therapy, Virology, MESH: Odds Ratio, Infectious Diseases, Logistic Models, Treatment Outcome, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Viral disease, Follow-Up Studies
Published
2000

18. Predominant intracellular expression of CXCR4 and CCR5 in purified primary trophoblast cells from first trimester and term human placentae

Author

Maldonado-Estrada, J., Elisabeth Menu, Roques, P., Vaslin, B., Dautry-Varsat, A., Barre-Sinoussi, F., Chaouat, G., Cytokines et immunorégulation, Institut National de la Santé et de la Recherche Médicale (INSERM), Grupo de Reproducción Animal, Escuela de Medicina Veterinaria, Biologie des Rétrovirus, Institut Pasteur [Paris] (IP), Laboratoire de Neuro-Immuno-Virologie, Service de Neurovirologie EMI E-01 (UMR E01), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Biologie des Interactions Cellulaires, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Intracellular Fluid, Receptors, CXCR4, Receptors, CCR5, MESH: Trophoblasts, Placenta, Pregnancy Trimester, Third, MESH: Flow Cytometry, MESH: Microscopy, Fluorescence, Cell Separation, In Vitro Techniques, MESH: Receptors, CCR5, MESH: Cell Separation, MESH: Receptors, CXCR4, MESH: Cell Compartmentation, MESH: Pregnancy, Pregnancy, Humans, MESH: Humans, MESH: Intracellular Fluid, Cell Membrane, fungi, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Flow Cytometry, MESH: Placenta, Cell Compartmentation, Trophoblasts, Pregnancy Trimester, First, Microscopy, Fluorescence, MESH: Pregnancy Trimester, Third, Female, MESH: Pregnancy Trimester, First, MESH: Female, MESH: Cell Membrane
Abstract

PROBLEM: The aim of the present study was to define the expression of CXCR4 and CCR5 on non-cultured non-stimulated primary human trophoblast cells (TCs) immediately after their immunopurification. METHOD OF STUDY: We have evaluated by flow cytometric analysis and immunofluorescence, highly purified primary TCs prepared from first trimester (8.2 +/- 0.3 weeks, n = 15) and term (Caesarean section, n = 10) placentae for the cell surface and intracellular expression of CXCR4 and CCR5. RESULTS: There was a high level of individual variability for CXCR4 and CCR5 expression between trophoblast batches. In first trimester and term placentae TCs, we found a greater number of TCs preparations expressing intracellular CXCR4 than CCR5 (P < 0.05). Both receptors were predominantly localized in the intracellular compartment of TCs, whatever if isolated from first trimester or term placentae. CONCLUSIONS: The functional consequences of the predominance of CXCR4 expression and of cellular addressing are briefly discussed.

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