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1. SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends

Author

Allouch, Awatef, Di Primio, Cristina, Paoletti, Audrey, Lê-Bury, Gabrielle, Subra, Frédéric, Quercioli, Valentina, Nardacci, Roberta, David, Annie, Saïdi, Héla, Cereseto, Anna, Ojcius, David M, Montagnac, Guillaume, Niedergang, Florence, Pancino, Gianfranco, Saez-Cirion, Asier, Piacentini, Mauro, Gougeon, Marie-Lise, Kroemer, Guido, and Perfettini, Jean-Luc

Subjects
HIV/AIDS, Infectious Diseases, Genetics, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Acetylation, Active Transport, Cell Nucleus, Anti-HIV Agents, Cell Cycle Proteins, Drug Resistance, Viral, HIV Infections, HIV-1, Humans, Microtubule-Associated Proteins, Microtubules, Raltegravir Potassium, Virus Replication, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology
Abstract

Understanding the viral-host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections and in permissive host cells. We found that SUGT1 determines the permissiveness to infection of lymphocytes and macrophages by modulating the nuclear import of the viral genome. More importantly, SUGT1 stabilizes the microtubule plus-ends (+MTs) of host cells (through the modulation of microtubule acetylation and the formation of end-binding protein 1 (EB1) comets). This effect on microtubules favors HIV-1 retrograde trafficking and replication. SUGT1 depletion impairs the replication of HIV-1 patient primary isolates and mutant virus that is resistant to raltegravir antiretroviral agent. Altogether our results identify SUGT1 as a cellular factor involved in the post-entry steps of HIV-1 infection that may be targeted for new therapeutic approaches.

Published
2020

3. Metabolic plasticity of HIV-specific CD8+ T cells is associated with enhanced antiviral potential and natural control of HIV-1 infection

Author

Angin, Mathieu, Volant, Stevenn, Passaes, Caroline, Lecuroux, Camille, Monceaux, Valérie, Dillies, Marie-Agnès, Valle-Casuso, José Carlos, Pancino, Gianfranco, Vaslin, Bruno, Le Grand, Roger, Weiss, Laurence, Goujard, Cecile, Meyer, Laurence, Boufassa, Faroudy, Müller-Trutwin, Michaela, Lambotte, Olivier, and Sáez-Cirión, Asier

Published
2019
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11. HIV-1 hijacks the cell extracellular matrix to spread collectively and efficiently between T lymphocytes

Author

Inizan, Catherine, primary, Caillet, Marina, additional, Desrames, Alexandra, additional, Bomme, Perrine, additional, MALLET, Adeline, additional, Bourdic, Katia, additional, Lambotte, Olivier, additional, Boufassa, Faroudy, additional, Mesel-Lemoine, Mariana, additional, Tangy, Frederic, additional, Pancino, Gianfranco, additional, Mouquet, Hugo, additional, Lagache, thibault, additional, Dufour, Alexandre C, additional, Olivo-Marin, Jean-Christophe, additional, Rey, Felix A, additional, Saez-Cirion, Asier, additional, and Thoulouze, Maria-Isabel, additional

Published
2021
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17. LOSS AND REGAIN OF SIV CONTROL UPON CD8+ CELL DEPLETION IN VIVO IN SIV-CONTROLLER MACAQUES IS NOT ASSOCIATED WITH EFFICIENT SIV SPECIFIC CD8+ T-CELL RESPONSES: ABSTRACT #6

Author

Saez-Cirion, Asier, Bruel, Timothée, Hamimi, Chiraz, Dereuddre-Bosquet, Nathalie, Cosma, Antonio, Shin, So Youn, Corneau, Aurélien, Versmisse, Pierre, Torres, Claire, Delache, Benoît, Even, Sophie, Guenounou, Sabrina, Targat, Brice, Malleret, Benoît, Karlsson, Ingrid, Barré-Sinoussi, Françoise, Le Grand, Roger, Pancino, Gianfranco, and Vaslin, Bruno

Published
2013

18. A Comparison of Cell Activation, Exhaustion, and Expression of HIV Coreceptors and Restriction Factors in HIV-1- and HIV-2-Infected Nonprogressors

Author

Diallo, Mariama Sadjo, Samri, Assia, Charpentier, Charlotte, Bertine, Mélanie, Cheynier, Rémi, Thiébaut, Rodolphe, Matheron, Sophie, Collin, Fidéline, Braibant, Martine, Candotti, Daniel, Appay, Victor, Brun-Vézinet, Françoise, Chaghil, Nathalie, Descamps, Diane, Hosmalin, Anne, Pancino, Gianfranco, Manel, Nicolas, Marchand, Lucie, Pedroza-Martins, Livia, Sáez-Cirión, Asier, Agut, Henri, Clauvel, Jean-Pierre, Costagliola, Dominique, Debré, Patrice, Theodorou, Ioannis, Sicard, Didier, Viard, Jean-Paul, Barin, Francis, Vieillard, Vincent, Autran, Brigitte, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Laboratoire de Virologie, 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), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Equipe de Biostatistique, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie, santé publique et développement, Virus, pseudo-virus: Morphogénèse et Antigénicité, Université de Tours (UT)-EA3856, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-EA3856

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Ubiquitin-Protein Ligases, Immunology, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, West africa, HIV Long-Term Survivors, Antiviral Restriction Factors, Tripartite Motif Proteins, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, virus diseases, 3. Good health, 030104 developmental biology, Infectious Diseases, HIV-2, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cell activation
Abstract

Human immunodeficiency viruses induce rare attenuated diseases due either to HIV-1 in the exceptional long-term nonprogressors (LTNPs) or to HIV-2 in West Africa. To better understand characteristics of these two disease types we performed a multiplex comparative analysis of cell activation, exhaustion, and expression of coreceptors and restriction factors in CD4 T cells susceptible to harbor those viruses. We analyzed by flow cytometry the expression of HLA-DR, PD1, CCR5, CXCR6, SAMHD1, Blimp-1, and TRIM5α on CD4 T cell subsets from 10 HIV-1

Published
2020

20. HIV-specific antibodies but not T-cell responses are associated with protection in seronegative partners of HIV-1 infected individuals in Cambodia

Author

Nguyen, Marie, Pean, Polidy, Lopalco, Lucia, Nouhin, Janin, Phoung, Viseth, Ly, Nary, Vermisse, Pierre, Henin, Yvette, Barre-Sinoussi, Francoise, Burastero, Samuele E., Reynes, Jean-Marc, Carcelain, Guislaine, and Pancino, Gianfranco

Subjects
HIV infection -- Risk factors, HIV infection -- Care and treatment, T cells -- Research, Health
Abstract

The analyses of humoral and T-cell immune responses, in vitro susceptibility to HIV-1 infection, and B-chemokine production in a group of EU partners of HIV-1 infected individuals in a Cambodian population were carried out to identify factors protecting against HIV-1 infection. The contrast between the presence of HIV-specific lgA and the lack of detectable T-cell responses in peripheral blood from EUs supports the hypothesis that the induction of mucosal humoral responses might play a main role in conferring protection to sexually exposed individuals.

Published
2006

21. Biochemical and HIV-1 coreceptor properties of K26R, a new CCR5 variant in China's Sichuan population

Author

Ma, Liying, Theodorou, Oiannis, Dudoit, Yasmine, Shao, Yiming, Capoulade-Metay, Corinne, Tran, Ton, Debre, Patrice, Hui Xing, Bismuth, Geroges, Jiaping Chen, and Pancino, Gianfranco

Subjects
Chemokine receptors -- Research, Chinese -- Health aspects, HIV infection -- Research, Health
Abstract

Five chemokine receptor (CCR5) coding region variants are identified in a Chinese population. A study of the K26R chemokine receptor activity and HIV coreceptor properties compared with wild type CCR5 and G106R is also presented.

Published
2005

22. Conclusions

Author

Pancino, Gianfranco, primary, Silvestri, Guido, additional, and Fowke, Keith R., additional

Published
2012
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24. Contributors

Author

Ball, T. Blake, primary, Barré-Sinoussi, Françoise, additional, Biasin, Mara, additional, Blankson, Joel N., additional, Broliden, Kristina, additional, Buckheit, Robert W., additional, Card, Catherine M., additional, Clerici, Mario, additional, de Silva, Thushan, additional, Fellay, Jacques, additional, Fowke, Keith R., additional, Jacquelin, Béatrice, additional, Kaul, Rupert, additional, Kaur, Amitinder, additional, Kirchhoff, Frank, additional, Lambotte, Olivier, additional, Landay, Alan L., additional, Luo, Ma, additional, McLaren, Paul J., additional, Moysi, Eirini, additional, Müller-Trutwin, Michaela C., additional, Münch, Jan, additional, Pancino, Gianfranco, additional, Pandrea, Ivona, additional, Pereyra, Florencia, additional, Plummer, Francis A., additional, Rowland-Jones, Sarah, additional, Sáez-Cirión, Asier, additional, Schmitz, Jörn E., additional, Shearer, Gene M., additional, Silvestri, Guido, additional, Telenti, Amalio, additional, Walker, Bruce D, additional, and Zahn, Roland C., additional

Published
2012
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29. Optimal Maturation of the SIV-Specific CD8+ T Cell Response after Primary Infection Is Associated with Natural Control of SIV: ANRS SIC Study

Author

Passaes, Caroline, primary, Millet, Antoine, additional, Madelain, Vincent, additional, Monceaux, Valérie, additional, David, Annie, additional, Versmisse, Pierre, additional, Sylla, Naya, additional, Gostick, Emma, additional, Llewellyn-Lacey, Sian, additional, Price, David A., additional, Blancher, Antoine, additional, Dereuddre-Bosquet, Nathalie, additional, Desjardins, Delphine, additional, Pancino, Gianfranco, additional, Le Grand, Roger, additional, Lambotte, Olivier, additional, Müller-Trutwin, Michaela, additional, Rouzioux, Christine, additional, Guedj, Jérémie, additional, Avettand-Fenoel, Véronique, additional, Vaslin, Bruno, additional, and Sáez-Cirión, Asier, additional

Published
2020
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30. Optimal maturation of the SIV-specific CD8+ T-cell response after primary infection is associated with natural control of SIV. ANRS SIC study

Author

Passaes, Caroline, primary, Millet, Antoine, additional, Madelain, Vincent, additional, Monceaux, Valérie, additional, David, Annie, additional, Versmisse, Pierre, additional, Sylla, Naya, additional, Gostick, Emma, additional, Price, David A., additional, Blancher, Antoine, additional, Dereuddre-Bosquet, Nathalie, additional, Pancino, Gianfranco, additional, Grand, Roger Le, additional, Lambotte, Olivier, additional, Müller-Trutwin, Michaela, additional, Rouzioux, Christine, additional, Guedj, Jeremie, additional, Avettand-Fenoel, Veronique, additional, Vaslin, Bruno, additional, and Sáez-Cirión, Asier, additional

Published
2019
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39. HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry

Author

Paoletti, Audrey, primary, Allouch, Awatef, additional, Caillet, Marina, additional, Saïdi, Hela, additional, Subra, Frédéric, additional, Nardacci, Roberta, additional, Wu, Qiuji, additional, Muradova, Zeinaf, additional, Voisin, Laurent, additional, Raza, Syed Qasim, additional, Law, Frédéric, additional, Thoreau, Maxime, additional, Dakhli, Haithem, additional, Delelis, Olivier, additional, Poirier-Beaudouin, Béatrice, additional, Dereuddre-Bosquet, Nathalie, additional, Le Grand, Roger, additional, Lambotte, Olivier, additional, Saez-Cirion, Asier, additional, Pancino, Gianfranco, additional, Ojcius, David M., additional, Solary, Eric, additional, Deutsch, Eric, additional, Piacentini, Mauro, additional, Gougeon, Marie-Lise, additional, Kroemer, Guido, additional, and Perfettini, Jean-Luc, additional

Published
2019
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40. Host hindrance to HIV-1 replication in monocytes and macrophages

Author

Pancino Gianfranco and Bergamaschi Anna

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. HIV-1 can replicate in blood monocytes, although only a minor proportion of circulating monocytes harbor viral DNA. Resident macrophages in tissues can be infected and function as viral reservoirs. However, their susceptibility to infection, and their capacity to actively replicate the virus, varies greatly depending on the tissue localization and cytokine environment. The susceptibility of monocytes to HIV-1 infection in vitro depends on their differentiation status. Monocytes are refractory to infection and become permissive upon differentiation into macrophages. In addition, the capacity of monocyte-derived macrophages to sustain viral replication varies between individuals. Host determinants regulate HIV-1 replication in monocytes and macrophages, limiting several steps of the viral life-cycle, from viral entry to virus release. Some host factors responsible for HIV-1 restriction are shared with T lymphocytes, but several anti-viral mechanisms are specific to either monocytes or macrophages. Whilst a number of these mechanisms have been identified in monocytes or in monocyte-derived macrophages in vitro, some of them have also been implicated in the regulation of HIV-1 infection in vivo, in particular in the brain and the lung where macrophages are the main cell type infected by HIV-1. This review focuses on cellular factors that have been reported to interfere with HIV-1 infection in monocytes and macrophages, and examines the evidences supporting their role in vivo, highlighting unique aspects of HIV-1 restriction in these two cell types.

Published
2010
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41. Localization of HIV-1 Vpr to the nuclear envelope: Impact on Vpr functions and virus replication in macrophages

Author

Bouaziz Serge, Bouchet Jérôme, Mazzolini Julie, David Annie, Le Rouzic Erwann, Jacquot Guillaume, Niedergang Florence, Pancino Gianfranco, and Benichou Serge

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background HIV-1 Vpr is a dynamic protein that primarily localizes in the nucleus, but a significant fraction is concentrated at the nuclear envelope (NE), supporting an interaction between Vpr and components of the nuclear pore complex, including the nucleoporin hCG1. In the present study, we have explored the contribution of Vpr accumulation at the NE to the Vpr functions, including G2-arrest and pro-apoptotic activities, and virus replication in primary macrophages. Results In order to define the functional role of Vpr localization at the NE, we have characterized a set of single-point Vpr mutants, and selected two new mutants with substitutions within the first α-helix of the protein, Vpr-L23F and Vpr-K27M, that failed to associate with hCG1, but were still able to interact with other known relevant host partners of Vpr. In mammalian cells, these mutants failed to localize at the NE resulting in a diffuse nucleocytoplasmic distribution both in HeLa cells and in primary human monocyte-derived macrophages. Other mutants with substitutions in the first α-helix (Vpr-A30L and Vpr-F34I) were similarly distributed between the nucleus and cytoplasm, demonstrating that this helix contains the determinants required for localization of Vpr at the NE. All these mutations also impaired the Vpr-mediated G2-arrest of the cell cycle and the subsequent cell death induction, indicating a functional link between these activities and the Vpr accumulation at the NE. However, this localization is not sufficient, since mutations within the C-terminal basic region of Vpr (Vpr-R80A and Vpr-R90K), disrupted the G2-arrest and apoptotic activities without altering NE localization. Finally, the replication of the Vpr-L23F and Vpr-K27M hCG1-binding deficient mutant viruses was also affected in primary macrophages from some but not all donors. Conclusion These results indicate that the targeting of Vpr to the nuclear pore complex may constitute an early step toward Vpr-induced G2-arrest and subsequent apoptosis; they also suggest that Vpr targeting to the nuclear pore complex is not absolutely required, but can improve HIV-1 replication in macrophages.

Published
2007
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42. Persistent resistance to HIV-1 infection in CD4 T cells from exposed uninfected Vietnamese individuals is mediated by entry and post-entry blocks

Author

Barré-Sinoussi Françoise, Carpentier Wassila, Chakrabarti Lisa A, Truong Lien X, Versmisse Pierre, Sáez-Cirión Asier, Scott-Algara Daniel, and Pancino Gianfranco

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background We have previously reported that CD4 T cells from some exposed uninfected (EU) Vietnamese intravenous drug users are relatively resistant to HIV infection in vitro. Here, we further characterized the restriction of viral replication in CD4 T cells from five EUs and assessed its persistence in serial samples. Results CD4 T cells and/or PBMC sampled during a period of between 2 and 6 years were challenged with replication-competent HIV-1 and other retroviral particles pseudotyped with envelope proteins of various tropisms. CCR5 expression and function in resistant CD4 T cells was evaluated. The step at which HIV-1 replication is restricted was investigated by real-time PCR quantification of HIV-1 reverse transcripts. We identified three patterns of durable HIV-1 restriction in EU CD4 T cells. CD4 T cells from four of the five EU subjects were resistant to HIV-1 R5 infection. In two cases this resistance was associated with low CCR5 surface expression, which was itself associated with heterozygous CCR5 mutations. In the other two cases, CD4 T cells were resistant to HIV-1 R5 infection despite normal CCR5 expression and signaling function, and normal β-chemokine secretion upon CD4 T cell activation. Instead, restriction appeared to be due to enhanced CD4 T cell sensitivity to β-chemokines in these two subjects. In the fifth EU subject the restriction involved post-entry steps of viral replication and affected not only HIV-1 but also other lentiviruses. The restriction was not overcome by a high viral inoculum, suggesting that it was not mediated by a saturable inhibitory factor. Conclusion Various constitutive mechanisms of CD4 T cell resistance to HIV-1 infection, affecting entry or post-entry steps of viral replication, are associated with resistance to HIV-1 in subjects who remain uninfected despite long-term high-risk behavior.

Published
2006
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43. Reduced CD4 T cell activation and in vitro susceptibility to HIV-1 infection in exposed uninfected Central Africans

Author

Fontanet Arnaud, Breton Guillaume, Versmisse Pierre, Léal Josianne, Ipero Julienne, Marechal Valéry, Chartier Loïc, Bégaud Evélyne, Capoulade-Metay Corinne, Fleury Hervé, Barré-Sinoussi Françoise, Scott-Algara Daniel, and Pancino Gianfranco

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Environmentally driven immune activation was suggested to contribute to high rates of HIV-1 infection in Africa. We report here a study of immune activation markers and susceptibility to HIV-1 infection in vitro of forty-five highly exposed uninfected partners (EUs) of HIV-1 infected individuals in Central African Republic, in comparison with forty-four low-risk blood donors (UCs). Results Analysis of T lymphocyte subsets and activation markers in whole blood showed that the absolute values and the percentage of HLA-DR+CD4 T cells and of CCR5+CD4 T cells were lower in the EUs than in the UCs (p = 0.0001). Mutations in the CCR5 coding region were not found in either group. Susceptibility to in vitro infection of unstimulated peripheral blood mononuclear cells, prior of PHA activation, was decreased in EUs compared to UCs, either using a CXCR4-tropic or a CCR5-tropic HIV-1 strain (p = 0.02 and p = 0.05, respectively). Levels of MIP-1β, but not of MIP-1α or RANTES, in the supernatants of PHA-activated PBMC, were higher in the EUs than in the UCs (p = 0.007). Conclusion We found low levels of CD4 T cell activation and reduced PBMC susceptibility to HIV-1 infection in Central African EUs, indicating that both may contribute to the resistance to HIV-1 infection.

Published
2006
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44. First Dominique Dormont international conference on 'Host-pathogen interactions in chronic infections – viral and host determinants of HCV, HCMV, and HIV infections'

Author

Boutboul Françoise, Mabondzo Aloïse M, Samri Assia, Gras Gabriel S, Inchauspé Geneviève, Bain Christine, Saez-Cirion Asier, Pancino Gianfranco, Müller-Trutwin Mickaela C, Menu Elisabeth, and Grand Roger Le

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract The first Dominique Dormont International Conference on "Viral and host determinantsof HCV, HCMV, and HIV infections "was held in Paris, Val-de-Grâce, on December 3–4, 2004. The following is a summary of the scientific sessions of this meeting (http://www.congres-evenement.fr/ddormont).

Published
2005
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45. p21 Restricts HIV-1 in Monocyte-Derived Dendritic Cells through the Reduction of Deoxynucleoside Triphosphate Biosynthesis and Regulation of SAMHD1 Antiviral Activity VIRUS-CELL INTERACTIONS crossm

Author

Valle-Casuso, Jose Carlos, Allouch, Awatef, David, Annie, Lenzi, Gina, Studdard, Lydia, Barré-Sinoussi, Françoise, Muller-Trutwin, Michaela, Kim, Baek, Pancino, Gianfranco, Saez-Cirion, Asier, HIV, Inflammation et persistance, Institut Pasteur [Paris], Régulation des Infections Rétrovirales, Emory University [Atlanta, GA], This study was funded by grants from Sidaction (France) to A.S.-C. and the National Institutes of Health (NIH), grants R01 GM104198 and R01 AI049781-01AI049781, to B.K. J.C.V.-C. received postdoctoral financial support from Sidaction and the Roux-Cantarini program at the Institut Pasteur. A.A. received a postdoctoral fellowship from Sidaction, We are grateful to Alexandra Cribier for kindly providing the pSAMHD1 antibody, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, and Institut Pasteur [Paris] (IP)

Subjects
MESH: Antiviral Agents, MESH: Humans, p21, MESH: Dendritic Cells, MESH: Deoxyribonucleotides, cellular factors, MESH: Virus Replication, MESH: DNA Replication, MESH: SAM Domain and HD Domain-Containing Protein 1, MESH: Monocytes, SAMHD1, MESH: Cyclin-Dependent Kinase Inhibitor p21, dNTPs, MESH: HIV-1, HIV replication, MESH: Polyphosphates, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, dendritic cells
Abstract

International audience; HIV-1 infection of noncycling cells, such as dendritic cells (DCs), is impaired due to limited availability of deoxynucleoside triphosphates (dNTPs), which are needed for HIV-1 reverse transcription. The levels of dNTPs are tightly regulated during the cell cycle and depend on the balance between dNTP biosynthesis and degradation. SAMHD1 potently blocks HIV-1 replication in DCs, although the underlying mechanism is still unclear. SAMHD1 has been reported to be able to degrade dNTPs and viral nucleic acids, which may both hamper HIV-1 reverse transcription. The relative contribution of these activities may differ in cycling and noncycling cells. Here, we show that inhibition of HIV-1 replication in monocyte-derived DCs (MDDCs) is associated with an increased expression of p21cip1/waf, a cell cycle regulator that is involved in the differentiation and maturation of DCs. Induction of p21 in MDDCs decreases the pool of dNTPs and increases the antiviral active isoform of SAMHD1. Although both processes are complementary in inhibiting HIV-1 replica-tion, the antiviral activity of SAMHD1 in our primary cell model appears to be, at least partially, independent of its dNTPase activity. The reduction in the pool of dNTPs in MDDCs appears rather mostly due to a p21-mediated suppression of several enzymes involved in dNTP synthesis (i.e., RNR2, TYMS, and TK-1). These results are important to better understand the interplay between HIV-1 and DCs and may inform the design of new therapeutic approaches to decrease viral dissemination and improve immune responses against HIV-1. IMPORTANCE DCs play a key role in the induction of immune responses against HIV. However, HIV has evolved ways to exploit these cells, facilitating immune evasion and virus dissemination. We have found that the expression of p21, a cyclin-dependent kinase inhibitor involved in cell cycle regulation and monocyte differentiation and maturation, potentially can contribute to the inhibition of HIV-1 replication in monocyte-derived DCs through multiple mechanisms. p21 decreased the size of the intracellular dNTP pool. In parallel, p21 prevented SAMHD1 phos-phorylation and promoted SAMHD1 dNTPase-independent antiviral activity. Thus, induction of p21 resulted in conditions that allowed the effective inhibition of HIV-1 replication through complementary mechanisms. Overall, p21 appears to be a key regulator of HIV infection in myeloid cells.

Published
2017

46. High eomesodermin expression among CD57+ CD8+ T cells identifies a CD8+ T cell subset associated with viral control during chronic human immunodeficiency virus infection

Author

Simonetta, Federico, Hua, Stéphane, Lecuroux, Camille, Gérard, Sandie, Boufassa, Faroudy, Saez-Cirion, Asier, Pancino, Gianfranco, Goujard, Cécile, Lambotte, Olivier, Venet, Alain, Bourgeois, Christine, Guibert, Marie-Genevieve, INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), Service de médecine interne, immunologie clinique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the Agence Nationale de la recherche contre le SIDA et les hépatites virales (ANRS) and Fondation de France. Federico Simonetta was also supported by the Fondation pour la recherche médicale (FRM)., Hôpital Universitaire de Genève, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Institut Pasteur [Paris]

Subjects
ddc:616, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cellular Response to Infection, HIV Infections, CD8-Positive T-Lymphocytes, Middle Aged, HIV Infections/immunology/virology, CD57 Antigens, T-Box Domain Proteins/metabolism, CD8-Positive T-Lymphocytes/virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, Antigens, T-Box Domain Proteins, CD57, Antigens, CD57/immunology
Abstract

International audience; During HIV infection, increased CD57 expression among CD8(+) T cells has been associated with immune senescence and defective immune responses. Interestingly, CD57-expressing CD8(+) T cells exhibit a dual profile, being simultaneously highly cytotoxic (terminally differentiated effectors) and poorly proliferative (replicative senescent). Recent publications point toward a positive role of CD57-expressing CD8(+) T cell subsets, presumably due to their high cytolytic activity. We further investigated the phenotype of CD57-expressing CD8(+) T cells in healthy donors and during HIV infection combining CD57 expression to Eomesodermin (EOMES), a T box transcription factor which determines, coordinately with T-bet, effector and memory CD8(+) T cell differentiation. We defined in healthy donors two functionally distinct CD57-expressing CD8(+) T cell subsets exhibiting different levels of EOMES expression: EOMES(hi) CD57(+) and EOMES(int) CD57(+) CD8(+) T cells. EOMES(hi) CD57(+) cells exhibited low cytotoxic activity but preserved proliferative capacity and interleukin 7 (IL-7) receptor expression, whereas EOMES(int) CD57(+) cells exhibited obvious cytotoxic functions and a more terminally differentiated phenotype. We next performed a similar analysis in different contexts of HIV infection: primary infected patients, long-term viremic patients, aviremic patients treated with antiretroviral therapy, and HIV controllers; we demonstrated a higher percentage of CD57-expressing cells in all HIV-infected patients regardless of virological status. When heterogeneity in EOMES expression among CD57 cells was taken into account, we detected significantly higher proportions of EOMES(hi) CD57(+) cells among HIV-specific and nonspecific CD8(+) T cells from HIV controllers than in aviremic antiretroviral-treated patients and viremic patients. Importantly, such a peculiar non-terminally differentiated EOMES(hi) CD57(+) phenotypic profile was associated with viral control. Importance: This study demonstrates that functional heterogeneity exists among CD57-expressing CD8 T cells, which include both terminally differentiated, highly cytotoxic EOMES(int) CD57(+) CD8(+) T cells and less differentiated EOMES(hi) CD57(+) CD8 T cells, which do not exhibit immediate cytotoxic functions but present high proliferative capacity. Interestingly, HIV controllers present a high proportion of EOMES(hi) CD57 cells among CD57-expressing HIV-specific CD8 T cells compared to both long-term viremic and aviremic antiretroviral therapy (ART)-treated patients, suggesting a beneficial role for this cell subset in viral control.

Published
2014

47. Proceedings of the Frontiers of Retrovirology Conference 2016

Author

Zurnic, Irena, primary, Hütter, Sylvia, additional, Lehmann, Ute, additional, Stanke, Nicole, additional, Reh, Juliane, additional, Kern, Tobias, additional, Lindel, Fabian, additional, Gerresheim, Gesche, additional, Hamann, Martin, additional, Müllers, Erik, additional, Lesbats, Paul, additional, Cherepanov, Peter, additional, Serrao, Erik, additional, Engelman, Alan, additional, Lindemann, Dirk, additional, Da Silva Santos, Claire, additional, Tartour, Kevin, additional, Cimarelli, Andrea, additional, Burdick, Rya, additional, Chen, Jianbo, additional, Sastri, Jaya, additional, Hu, Wei-Shau, additional, Pathak, Vinay, additional, Keppler, Oliver T., additional, Pradeau, Karine, additional, Eiler, Sylvia, additional, Levy, Nicolas, additional, Lennon, Sarah, additional, Cianferani, Sarah, additional, Emiliani, Stéphane, additional, Ruff, Marc, additional, Parissi, Vincent, additional, Rato, Sylvie, additional, Rausell, Antonio, additional, Munoz, Miguel, additional, Telenti, Amalio, additional, Ciuffi, Angela, additional, Zhyvoloup, Alexander, additional, Melamed, Anat, additional, Anderson, Ian, additional, Planas, Delphine, additional, Kriston-Vizi, Janos, additional, Ketteler, Robin, additional, Lee, Chen- Hsuin, additional, Merritt, Andy, additional, Ancuta, Petronela, additional, Bangham, Charles, additional, Fassati, Ariberto, additional, Rodari, Anthony, additional, Van Driessche, Benoit, additional, Galais, Mathilde, additional, Delacourt, Nadége, additional, Fauquenoy, Sylvain, additional, Vanhulle, Caroline, additional, Kula, Anna, additional, Burny, Arsène, additional, Rohr, Olivier, additional, Van Lint, Carine, additional, van Montfort, Thijs, additional, van der Sluis, Renee, additional, Speijer, Dave, additional, Berkhout, Ben, additional, Meng, Bo, additional, Rutkowski, Andrzej, additional, Berry, Neil, additional, Dölken, Lars, additional, Lever, Andrew, additional, Schuster, Thomas, additional, Asbach, Benedikt, additional, Wagner, Ralf, additional, Gross, Christine, additional, Wiesmann, Veit, additional, Kalmer, Martina, additional, Wittenberg, Thomas, additional, Gettemans, Jan, additional, Thoma-Kress, Andrea K., additional, Li, Minghua, additional, Freed, Eric O., additional, Liu, Shan-Lu, additional, Müller, Janis, additional, Münch, Jan, additional, Sewald, Xaver, additional, Uchil, Pradeep, additional, Ladinsky, Mark, additional, Beloor, Jagadish, additional, Pi, Ruoxi, additional, Herrmann, Christin, additional, Motamedi, Nasim, additional, Murooka, Thomas, additional, Brehm, Michael, additional, Greiner, Dale, additional, Mempel, Thorsten, additional, Bjorkman, Pamela, additional, Kumar, Priti, additional, Mothes, Walther, additional, Joas, Simone, additional, Parrish, Erica, additional, Gnanadurai, Clement Wesley, additional, Lump, Edina, additional, Stürzel, Christina M., additional, Parrish, Nicholas F., additional, Sauermann, Ulrike, additional, Töpfer, Katharina, additional, Schultheiss, Tina, additional, Bosinger, Steven, additional, Silvestri, Guido, additional, Apetrei, Cristian, additional, Huot, Nicholas, additional, Müller-Trutwin, Michaela, additional, Sauter, Daniel, additional, Hahn, Beatrice H., additional, Stahl-Hennig, Christiane, additional, Kirchhoff, Frank, additional, Schumann, Gerald, additional, Jung-Klawitter, Sabine, additional, Fuchs, Nina V., additional, Upton, Kyle R., additional, Muñoz-Lopez, Martin, additional, Shukla, Ruchi, additional, Wang, Jichang, additional, Garcia-Canadas, Marta, additional, Lopez-Ruiz, Cesar, additional, Gerhardt, Daniel J., additional, Sebe, Attila, additional, Grabundzija, Ivana, additional, Gerdes, Patricia, additional, Merkert, Sylvia, additional, Pulgarin, Andres, additional, Bock, Anja, additional, Held, Ulrike, additional, Witthuhn, Anett, additional, Haase, Alexandra, additional, Wolvetang, Ernst J., additional, Martin, Ulrich, additional, Ivics, Zoltán, additional, Izsvák, Zsuzsanna, additional, Garcia-Perez, J., additional, Faulkner, Geoffrey J., additional, Hurst, Tara, additional, Katzourakis, Aris, additional, Magiorkinis, Gkikas, additional, Schott, Kerstin, additional, Derua, Rita, additional, Seifried, Janna, additional, Reuter, Andreas, additional, Schmitz, Heike, additional, Tondera, Christiane, additional, Brandariz-Nuñez, Alberto, additional, Diaz-Griffero, Felipe, additional, Janssens, Veerle, additional, König, Renate, additional, Baldauf, Hanna-Mari, additional, Stegmann, Lena, additional, Schwarz, Sarah-Marie, additional, Trotard, Maud, additional, Martin, Margarethe, additional, Lenzi, Gina, additional, Burggraf, Manja, additional, Pan, Xiaoyu, additional, Fregoso, Oliver I., additional, Lim, Efrem S., additional, Abraham, Libin, additional, Erikson, Elina, additional, Nguyen, Laura, additional, Ambiel, Ina, additional, Rutsch, Frank, additional, Kim, Baek, additional, Emerman, Michael, additional, Fackler, Oliver T., additional, Wittmann, Sabine, additional, Behrendt, Rayk, additional, Volkmann, Bianca, additional, Eissmann, Kristin, additional, Gramberg, Thomas, additional, Bolduan, Sebastian, additional, Koppensteiner, Herwig, additional, Regensburg, Stefanie, additional, Brack-Werner, Ruth, additional, Draenert, Rika, additional, Schindler, Michael, additional, Ducroux, Aurélie, additional, Xu, Shuting, additional, Ponnurangam, Aparna, additional, Franz, Sergej, additional, Malassa, Angelina, additional, Ewald, Ellen, additional, Goffinet, Christine, additional, Fung, Sin-Yee, additional, Chan, Ching-Ping, additional, Yuen, Chun-Kit, additional, Kok, Kin-Hang, additional, Chan, Chin-Ping, additional, Jin, Dong-Yan, additional, Dittmer, Ulf, additional, Kmiec, Dorota, additional, Iyer, Shilpa, additional, Stürzel, Christina, additional, Hahn, Beatrice, additional, Ariumi, Yasuo, additional, Yasuda-Inoue, Mariko, additional, Kawano, Koudai, additional, Tateishi, Satoshi, additional, Turelli, Priscilla, additional, Compton, Alex, additional, Roy, Nicolas, additional, Porrot, Françoise, additional, Billet, Anne, additional, Casartelli, Nicoletta, additional, Yount, Jacob, additional, Liang, Chen, additional, Schwartz, Oliver, additional, Magnus, Carsten, additional, Reh, Lucia, additional, Moore, Penny, additional, Uhr, Therese, additional, Weber, Jacqueline, additional, Morris, Lynn, additional, Trkola, Alexandra, additional, Grindberg, Rashel V., additional, Schlaepfer, Erika, additional, Schreiber, Gideon, additional, Simon, Viviana, additional, Speck, Roberto F., additional, Debyser, Zeger, additional, Vranckx, Lenard, additional, Demeulemeester, Jonas, additional, Saleh, Suha, additional, Verdin, Eric, additional, Cereseto, Anna, additional, Christ, Frauke, additional, Gijsbers, Rik, additional, Wang, Gang, additional, Zhao, Na, additional, Das, Atze T., additional, Köstler, Josef, additional, Perdiguero, Beatriz, additional, Esteban, Mariano, additional, Jacobs, Bertram L., additional, Montefiori, David C., additional, LaBranche, Celia C., additional, Yates, Nicole L., additional, Tomaras, Georgia D., additional, Ferrari, Guido, additional, Foulds, Kathryn E., additional, Roederer, Mario, additional, Landucci, Gary, additional, Forthal, Donald N., additional, Seaman, Michael S., additional, Hawkins, Natalie, additional, Self, Steven G., additional, Phogat, Sanjay, additional, Tartaglia, James, additional, Barnett, Susan W., additional, Burke, Brian, additional, Cristillo, Anthony D., additional, Ding, Song, additional, Heeney, Jonathan L., additional, Pantaleo, Giuseppe, additional, Stab, Viktoria, additional, Ensser, Armin, additional, Tippler, Bettina, additional, Burton, Dennis, additional, Tenbusch, Matthias, additional, Überla, Klaus, additional, Alter, Galit, additional, Lofano, Giuseppe, additional, Dugast, Anne-Sophie, additional, Kulkarni, Viraj, additional, Suscovich, Todd, additional, Opazo, Tatiana, additional, Barraza, Felipe, additional, Herrera, Diego, additional, Garces, Andrea, additional, Schwenke, Tomas, additional, Tapia, Diego, additional, Cancino, Jorge, additional, Arriagada, Gloria, additional, Haußner, Christina, additional, Damm, Dominik, additional, Rohrhofer, Anette, additional, Schmidt, Barbara, additional, Eichler, Jutta, additional, Midgley, Rebecca, additional, Wheeldon, James, additional, Piguet, Vincent, additional, Khopkar, Priyanka, additional, Rohamare, Megha, additional, Kulkarni, Smita, additional, Godinho-Santos, Ana, additional, Hance, Allan, additional, Goncalves, Joao, additional, Mammano, Fabrizio, additional, Gasser, Romain, additional, Hamoudi, Meriem, additional, Pellicciotta, Martina, additional, Zhou, Zhicheng, additional, Visdeloup, Clara, additional, Colin, Philippe, additional, Braibant, Martine, additional, Lagane, Bernard, additional, Negroni, Matteo, additional, Wamara, Jula, additional, Bannert, Norbert, additional, Mesplede, Thibault, additional, Osman, Nathan, additional, Anstett, Kaitlin, additional, Liang, Jiaming Calvin, additional, Pham, Hanh Thi, additional, Wainberg, Mark, additional, Shao, Wei, additional, Shan, Jigui, additional, Kearney, Mary, additional, Wu, Xiaolin, additional, Maldarelli, Frank, additional, Mellors, John, additional, Luke, Brian, additional, Coffin, John, additional, Hughes, Stephen, additional, Fricke, Thomas, additional, Opp, Silvana, additional, Shepard, Caitlin, additional, Ivanov, Dmitri, additional, Valle-Casuso, Jose, additional, Kanja, Marine, additional, Cappy, Pierre, additional, Lener, Daniela, additional, Knyazhanskaya, Ekaterina, additional, Anisenko, Andrey, additional, Zatsepin, Timofey, additional, Gottikh, Marina, additional, Komkov, Alexander, additional, Minervina, Anastasia, additional, Nugmanov, Gaiaz, additional, Nazarov, Vadim, additional, Khodosevich, Konstantin, additional, Mamedov, Ilgar, additional, Lebedev, Yuri, additional, Colomer-Lluch, Marta, additional, Serra-Moreno, Ruth, additional, Sarracino, Ambra, additional, Gharu, Lavina, additional, Pasternak, Alexander, additional, Marcello, Alessandro, additional, McCartin, Ann Marie, additional, Kulkarni, Anurag, additional, Le Douce, Valentin, additional, Gautier, Virginie, additional, Baeyens, Ann, additional, Naessens, Evelien, additional, Van Nuffel, Anouk, additional, Weening, Karin, additional, Reilly, Anne- Marie, additional, Claeys, Eva, additional, Trypsteen, Wim, additional, Vandekerckhove, Linos, additional, Eyckerman, Sven, additional, Gevaert, Kris, additional, Verhasselt, Bruno, additional, Mok, Hoi Ping, additional, Norton, Nicholas, additional, Fun, Axel, additional, Hirst, Jack, additional, Wills, Mark, additional, Miklik, Dalibor, additional, Senigl, Filip, additional, Hejnar, Jiri, additional, Sakuragi, Jun-ichi, additional, Sakuragi, Sayuri, additional, Yokoyama, Masaru, additional, Shioda, Tatsuo, additional, Sato, Hironori, additional, Bodem, Jochen, additional, Moschall, Rebecca, additional, Denk, Sarah, additional, Erkelenz, Steffen, additional, Schenk, Christian, additional, Schaal, Heiner, additional, Donhauser, Norbert, additional, Socher, Ellen, additional, Millen, Sebastian, additional, Sticht, Heinrich, additional, Mann, Melanie, additional, Wei, Guochao, additional, Betts, Matthew J., additional, Liu, Yang, additional, Kehl, Timo, additional, Russell, Robert B., additional, Löchelt, Martin, additional, Hohn, Oliver, additional, Mostafa, Saeed, additional, Hanke, Kirsten, additional, Norley, Stephen, additional, Chen, Chia-Yen, additional, Shingai, Masashi, additional, Borrego, Pedro, additional, Taveira, Nuno, additional, Strebel, Klaus, additional, Hellmund, Chris, additional, Friedrich, Melanie, additional, Hahn, Friedrich, additional, Setz, Christian, additional, Rauch, Pia, additional, Fraedrich, Kirsten, additional, Matthaei, Alina, additional, Henklein, Petra, additional, Traxdorf, Maximilian, additional, Fossen, Torgils, additional, Schubert, Ulrich, additional, Khwaja, Aya, additional, Galilee, Meytal, additional, Alian, Akram, additional, Schwalbe, Birco, additional, Hauser, Heiko, additional, Schreiber, Michael, additional, Scherpenisse, Mirte, additional, Cho, Young-Keol, additional, Kim, Jungeun, additional, Jeong, Daeun, additional, Trejbalova, Katerina, additional, Benesova, Martina, additional, Kucerova, Dana, additional, Vernerova, Zdenka, additional, Amouroux, Rachel, additional, Hajkova, Petra, additional, Elleder, Daniel, additional, Hron, Tomas, additional, Farkasova, Helena, additional, Padhi, Abinash, additional, Paces, Jan, additional, Zhu, Henan, additional, Gifford, Robert, additional, Murcia, Pablo, additional, Carrozza, Maria Luisa, additional, Niewiadomska, Anna-Maria, additional, Mazzei, Maurizio, additional, Abi-Said, Mounir, additional, Hughes, Joseph, additional, Hué, Stéphane, additional, Obasa, Adetayo, additional, Jacobs, Graeme, additional, Engelbrecht, Susan, additional, Mack, Katharina, additional, Starz, Kathrin, additional, Geyer, Matthias, additional, Bibollet-Ruche, Frederic, additional, Leoz, Marie, additional, Plantier, Jean Christophe, additional, Argaw-Denboba, Ayele, additional, Balestrieri, Emanuela, additional, Serafino, Annalucia, additional, Bucci, Ilaria, additional, Cipriani, Chiara, additional, Spadafora, Corrado, additional, Sinibaldi-Vallebona, Paolo, additional, Matteucci, Claudia, additional, Jayashree, S. Nandi, additional, Neogi, Ujjwal, additional, Chhangani, Anil K., additional, Rathore, Shravan Sing, additional, Mathur, Bajrang R. J., additional, Abati, Adeyemi, additional, Koç, B. Taylan, additional, Oğuzoğlu, Tuba Çiğdem, additional, Shimauchi, Takatoshi, additional, Caucheteux, Stephan, additional, Turpin, Jocelyn, additional, Finsterbusch, Katja, additional, Tokura, Yoshiki, additional, Souriant, Shanti, additional, Balboa, Luciana, additional, Pingris, Karine, additional, Kviatcowsky, Denise, additional, Raynaud-Messina, Brigitte, additional, Cougoule, Céline, additional, Mercier, Ingrid, additional, Kuroda, Marcelo, additional, González-Montaner, Pablo, additional, Inwentarz, Sandra, additional, Moraña, Eduardo Jose, additional, del Carmen Sasiain, Maria, additional, Neyrolles, Olivier, additional, Maridonneau-Parini, Isabelle, additional, Lugo-Villarino, Geanncarlo, additional, Vérollet, Christel, additional, Herrmann, Alexandra, additional, Thomas, Dominique, additional, Bouzas, Nerea Ferreirós, additional, Lahaye, Xavier, additional, Bhargava, Anvita, additional, Satoh, Takeshi, additional, Gentili, Matteo, additional, Cerboni, Silvia, additional, Silvin, Aymeric, additional, Conrad, Cécile, additional, Ahmed-Belkacem, Hakim, additional, Rodriguez, Elisa C., additional, Guichou, Jean-François, additional, Bosquet, Nathalie, additional, Piel, Matthieu, additional, Le Grand, Roger, additional, King, Megan, additional, Pawlotsky, Jean-Michel, additional, Manel, Nicolas, additional, Hofmann, Henning, additional, Vanwalscappel, Benedicte, additional, Bloch, Nicolin, additional, Landau, Nathaniel, additional, Indik, Stanislav, additional, Hagen, Benedikt, additional, Valle-Casuso, José Carlos, additional, Allouch, Awatef, additional, David, Annie, additional, Barré-Sinoussi, Françoise, additional, Benkirane, Monsef, additional, Pancino, Gianfranco, additional, Saez-Cirion, Asier, additional, Lee, Wing-Yiu, additional, Sloan, Richard, additional, Schulte, Bianca, additional, Blomberg, Jonas, additional, Vargiu, Luana, additional, Rodriguez-Tomé, Patricia, additional, Tramontano, Enzo, additional, Sperber, Göran, additional, Kumari, Namita, additional, Ammosova, Tatiana, additional, Diaz, Sharmeen, additional, Oneal, Patricia, additional, Nekhai, Sergei, additional, Fahrny, Audrey, additional, Gers-Huber, Gustavo, additional, Audigé, Annette, additional, Jayaprakash, Anitha, additional, Sachidanandam, Ravi, additional, Hernandez, Matt, additional, Dillon-White, Marsha, additional, Maze, Emmanuel, additional, Ham, Claire, additional, Almond, Neil, additional, Towers, Greg, additional, Belshaw, Robert, additional, de Sousa-Pereira, Patrícia, additional, Abrantes, Joana, additional, Pizzato, Massimo, additional, Esteves, Pedro J., additional, Kahle, Tanja, additional, Schmitt, Sven, additional, Merkel, Laura, additional, Reuter, Nina, additional, Stamminger, Thomas, additional, Rosa, Ilaria Dalla, additional, Bishop, Kate, additional, Spinazzola, Antonella, additional, Groom, Harriet, additional, Vieyres, Gabrielle, additional, Müsken, Mathias, additional, Zillinger, Thomas, additional, Hornung, Veit, additional, Barchet, Winfried, additional, Häussler, Susanne, additional, Pietschmann, Thomas, additional, Javed, Aneela, additional, Leuchte, Nicole, additional, Salinas, Gabriela, additional, Opitz, Lennart, additional, Sopper, Sieghart, additional, Mummert, Christiane, additional, Hofmann, Christian, additional, Hückelhoven, Angela G., additional, Bergmann, Silke, additional, Müller-Schmucker, Sandra M., additional, Harrer, Ellen G., additional, Dörrie, Jan, additional, Schaft, Niels, additional, Harrer, Thomas, additional, Cardinaux, Laure, additional, Zahno, M.- L., additional, Vogt, H.- R., additional, Zanoni, R., additional, Bertoni, G., additional, Muenchhoff, Maximilian, additional, Goulder, Philip, additional, Keppler, Oliver, additional, Rebensburg, Stephanie, additional, Helfer, Markus, additional, Zhang, Yuwei, additional, Chen, Huicheng, additional, Bernier, Annie, additional, Gosselin, Annie, additional, Routy, Jean- Pierre, additional, Wöhrl, Birgitta, additional, Schneider, Anna, additional, Corona, Angela, additional, Spöring, Imke, additional, Jordan, Mareike, additional, Buchholz, Bernd, additional, Maccioni, Elias, additional, Di Santo, Roberto, additional, Schweimer, Kristian, additional, Schölz, Christian, additional, Weinert, Brian, additional, Wagner, Sebastian, additional, Beli, Petra, additional, Miyake, Yasuyuki, additional, Qi, Jun, additional, Jensen, Lars, additional, Streicher, Werner, additional, McCarthy, Anna, additional, Westwood, Nicholas, additional, Lain, Sonia, additional, Cox, Jürgen, additional, Matthias, Patrick, additional, Mann, Matthias, additional, Bradner, James, additional, Choudhary, Chunaram, additional, Stern, Marcel, additional, Valletta, Elena, additional, Frezza, Caterina, additional, Marino-Merlo, Francesca, additional, Grelli, Sandro, additional, Serafino, Anna Lucia, additional, Mastino, Antonio, additional, Macchi, Beatrice, additional, Kaulfuß, Meike, additional, Windmann, Sonja, additional, Bayer, Wibke, additional, Mikasi, Sello, additional, Heß, Rebecca, additional, Bonsmann, Michael Storcksdieck gen., additional, Kirschning, Carsten, additional, Lepenies, Bernd, additional, Kolenbrander, Anne, additional, Temchura, Vladimir, additional, Iijima, Kenta, additional, Kobayashi, Junya, additional, and Ishizaka, Yukihito, additional

Published
2016
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48. Long-Term Spontaneous Control of HIV-1 Is Related to Low Frequency of Infected Cells and Inefficient Viral Reactivation

Author

Noel, Nicolas, primary, Peña, Ruth, additional, David, Annie, additional, Avettand-Fenoel, Veronique, additional, Erkizia, Itziar, additional, Jimenez, Esther, additional, Lecuroux, Camille, additional, Rouzioux, Christine, additional, Boufassa, Faroudy, additional, Pancino, Gianfranco, additional, Venet, Alain, additional, Van Lint, Carine, additional, Martinez-Picado, Javier, additional, Lambotte, Olivier, additional, Sáez-Cirión, Asier, additional, and Prado, Julia G., additional

Published
2016
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49. CD8 T-cells from most HIV-infected patients lack ex vivo HIV-suppressive capacity during acute and early infection

Author

Lecuroux, Camille, Girault, Isabelle, Chéret, Antoine, Versmisse, Pierre, Nembot, Georges, Meyer, Laurence, Rouzioux, Christine, Pancino, Gianfranco, Venet, Alain, Saez-Cirion, Asier, trial, ANRS 147 OPTIPRIM, Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Université Paris Descartes - Paris 5 (UPD5), Service Universitaire de Maladies Infectieuses et du Voyageur, Centre Hospitalier Gustave Dron, Régulation des Infections Rétrovirales, Institut Pasteur [Paris], INSERM U1018, Faculté de Médecine Paris Sud, Institut National de la Santé et de la Recherche Médicale (INSERM), Departement d'épidémiologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The ANRS 147 OPTIPRIM trial was funded by ANRS (French National Agency for Research on AIDS and Viral Hepatitis) and conducted with the support of MSD, Janssen, ViiV Healthcare and Gilead. CL received a postdoctoral fellowship from ANRS. GP is an employee of INSERM (Institut National de la Santé et de la Recherche Médicale). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Guibert, Marie-Genevieve, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
CD4-Positive T-Lymphocytes, Male, Viral Diseases, Time Factors, lcsh:Medicine, HIV Infections, Adaptive Immunity, CD8-Positive T-Lymphocytes, Virus Replication, 0302 clinical medicine, Leukocytes, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Cytotoxic T cell, lcsh:Science, Immune Response, Cells, Cultured, 0303 health sciences, Multidisciplinary, Cultured, T Cells, virus diseases, Middle Aged, Viral Load, 3. Good health, Host-Pathogen Interaction, Infectious Diseases, Acute Disease, Disease Progression, Medicine, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Viral load, Research Article, medicine.drug, Interleukin 2, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immune Cells, Cells, Immunology, Mononuclear, Viremia, Biology, Microbiology, 03 medical and health sciences, medicine, Humans, Immunity to Infections, 030304 developmental biology, lcsh:R, Immunity, HIV, medicine.disease, Virology, Chronic infection, Viral replication, Leukocytes, Mononuclear, HIV-1, Interleukin-2, lcsh:Q, Ex vivo, CD8, 030215 immunology
Abstract

International audience; The strong CD8+ T-cell-mediated HIV-1-suppressive capacity found in a minority of HIV-infected patients in chronic infection is associated with spontaneous control of viremia. However, it is still unclear whether such capacities were also present earlier in the CD8+ T cells from non controller patients and then lost as a consequence of uncontrolled viral replication. We studied 50 patients with primary HIV-1-infection to determine whether strong CD8+ T-cell-mediated HIV suppression is more often observed at that time. Despite high frequencies of polyfunctional HIV-specific CD8+ T-cells and a strong CD4+ T-helper response, CD8+ T-cells from 48 patients lacked strong HIV-suppressive capacities ex vivo. This indicates that the superior HIV-suppressive capacity of CD8+ T-cells from HIV controllers is not a general characteristic of the HIV-specific CD8+ T cell response in primary HIV infection.

Published
2013

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