Homing, immune activation and infection

Molecular bases of human diseases

There is a growing amount of evidences in favor of causative links between a chronic state of overactivity of the immune system and the development of morbidities such as atherosclerosis, metabolic syndrome and type 2 diabetes, liver steatosis, neurocognitive disorders, osteoporosis, frailty, and even some types of cancer.
HIV infection is a relevant model to explore these causative links. Our team is working on the chronic immune activation observed in efficiently treated HIV-1 patients (virologic responders), and on its consequences. Our working hypothesis in that each virologic responder may be characterized by one out of a few profiles of immune activation. Each of these immune activation profiles could be driven by specific causes, including persistent HIV production, microbial translocation, coinfections, CD4 T cell lymphopenia, immune senescence, and/or Th17/Treg dysregulation. Moreover, each immune activation profile might fuel specific comorbidities.
Apart from driving chronic comorbidities, the persistence of immune activation in virologic responders may impede CD4 T cell recovery. We are currently exploring one mechanism linking monocyte activation to impaired CD4 T cell restoration.
Besides immune activation, another major concern for virologic responders today is the persistence of HIV genome in the so-called « reservoir cells ». Various latency-reversing agents (LRA) have been proposed to force these reservoir cells to produce virions, with the aim of inducing their destruction. After a systematic screening of G-protein coupled receptors (GPCR) coexpressed in CD4+ T cells with the HIV coreceptor CCR5, we have identified GPCR whose activation may result in reversing HIV latency.

figure 1 en

Figure 1. Virologic responders present with different immune activation profiles. Heatmap showing the hierarchical clustering of the activation markers (vertical) as well as of the virologic responders according to their profile of activation (horizontal). Each Profile number is indicated


Collaborations

  • Division of Hematology, McGill University Health Center, Montréal, Québec, Canada
  • Département des Maladies infectieuses et immunitaires, CHU Laval, Québec, Canada
  • INSERM U1065, Nice, France
  • Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France
  • Hôpital Saint-Antoine, Département de Santé Publique, AP-HP, Paris France
  • Université Paris Descartes, Sorbonne Paris Cité; AP-HP, CIC Cochin Pasteur, Hôpital Cochin, Paris, France
  • INSERM, CIC 1417, Paris, F-CRIN, I–REIVAC, France
36
CORBEAU Pierre
Researcher

149
METTLING Clement
Researcher

1493
KUNDURA Lucy
PhD Student

1954
SAHLI Wided
PhD Student

1934
KAMRAOUI Islay
Stagiaire

PUBLICATIONS OF THE TEAM

Two-drug vs. three-drug combinations for HIV-1: Do we have enough data to make the switch?

Moreno S, Perno CF, Mallon PW, Behrens G, Corbeau P, Routy JP, Darcis G

Increased Neutrophil Surface PD-L1 Expression in Tobacco Smokers: Consequences for Anti-PD-1 Treatment.

Psomas C, Tuaillon E, Marin G, Reynes J, Corbeau P

Immune activation, smoking, and vaccine response

Younas M, Carrat F, Finge S, Desaint C, Launay O, Corbeau P; ANRS HB03 VIHVAC-B Trial Group

Plasma Level of Soluble ST2 in Chronically Infected HIV-1 Patients with Suppressed Viremia

Younas M, Psomas C, Mehraj V, Cezar R, Portales P, Tuaillon E, Guigues A, Reynes J, Corbeau P, Routy JP.

Reversing HIV latency via sphingosine-1-phosphate receptor 1 signaling

Duquenne C, Gimenez S, Guigues A, Viala B, Boulouis C, Mettling C, Maurel D, Campos N, Doumazane E, Comps-Agrar L, Tazi J, Prézeau L, Corbeau P, François V.

Immune activation in the course of HIV-1 infection: Causes, phenotypes and persistence under therapy

Younas M, Psomas C, Reynes J, Corbeau P.

One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study

Psomas C, Younas M, Reynes C, Cezar R, Portalès P, Tuaillon E, Guigues A, Merle C, Atoui N, Fernandez C, Le Moing V, Barbuat C, Marin G, Nagot N, Sotto A, Eliaou JF, Sabatier R, Reynes J, Corbeau P

Autophagy-associated dengue vesicles promote viral transmission avoiding antibody neutralization

Wu YW, Mettling C, Wu SR, Yu CY, Perng GC, Lin YS, Lin YL

HIV-1 Tat inhibits phagocytosis by preventing the recruitment of Cdc42 to the phagocytic cup

Debaisieux S, Lachambre S, Gross A, Mettling C, Besteiro S, Yezid H, Henaff D, Chopard C, Mesnard JM, Beaumelle B.

The Two Human CXCR4 Isoforms Display Different HIV Receptor Activities: Consequences for the Emergence of X4 Strains

Duquenne C, Psomas C, Gimenez S, Guigues A, Carles MJ, Barbuat C, Lavigne JP, Sotto A, Reynes J, Guglielmi P, Mettling C, François V, Corbeau P

Maraviroc-induced decrease in circulating bacterial products is not linked to an increase in immune activation in HIV-infected individuals.

Psomas C, Lavigne JP, Barbuat C, Trabelsi S, Ghosn J, Lascoux-Combe C, Flandre P, Cuzin L, Reynes J, Autran B, Corbeau P.

Maraviroc intensification of stable antiviral therapy in HIV-1-infected patients with poor immune restoration: MARIMUNO-ANRS 145 study

Cuzin L, Trabelsi S, Delobel P, Barbuat C, Reynes J, Allavena C, Peytavin G, Ghosn J, Lascoux-Combe C, Psomas C, Corbeau P, Flandre P; the ANRS 145 MARIMUNO Study group.

Correction: Combined Phytochemistry and Chemotaxis Assays for Identification and Mechanistic Analysis of Anti-Inflammatory Phytochemicals in Fallopia japonica

Shen MY, Liu YJ, Don MJ, Liu HY, Chen ZW, Mettling C, Corbeau P, Chiang CK, Jang YS, Li TH, Young P, Chang CL, Lin YL, Yang WC

The intensity of immune activation is linked to the level of CCR5 expression in human immunodeficiency virus type 1-infected persons.

Portales P, Psomas KC, Tuaillon E, Mura T, Vendrell JP, Eliaou JF, Reynes J, Corbeau P.

Interleukin-7 induces HIV type 1 R5-to-X4 switch.

Brieu N, Portalès P, Carles MJ, Corbeau P.

Strategy for anti-aquaporin-4 auto-antibody identification and quantification using a new cell-based assay

De Vidi I, Boursier G, Delouche N, Portalès P, Cadars E, Bouthier M, Mettling C, Lin YL, Thouvenot E, Carlander B, Camu W, Antel JP, Bar-Or A, Zephir H, Vermersch P, De Seze J, Corbeau P, Eliaou JF, Vincent T.

Immune reconstitution under antiretroviral therapy: a new challenge in HIV-1 infection

Corbeau, P., Reynes, J.

Circulating human CD4+ T cells have intracellular pools of CCR5 molecules.

Guglielmi L, Gimenez S, Larroque M, Tong X, Portalès P, Corbeau P.

Combined Phytochemistry and Chemotaxis Assays for Identification and Mechanistic Analysis of Anti-Inflammatory Phytochemicals in Fallopia japonica.

Shen MY, Liu YJ, Don MJ, Liu HY, Chen ZW, Mettling C, Corbeau P, Chiang CK, Jang YS, Li TH, Young P, Chang CL, Lin YL, Yang WC.

Pairwise Comparison of Isogenic HIV-1 Viruses: R5 Phenotype Replicates More Efficiently Than X4 Phenotype in Primary CD4+ T Cells Expressing Physiological Levels of CXCR4

Fiser AL, Lin YL, Portalès P, Mettling C, Clot J, Corbeau P.

Mesenchymal stem cell-dependent formation of heterotopic tendon-bone insertions (osteotendinous junctions)

Shahab-Osterloh, S., Witte, F., Hoffmann, A., Winkel, A., Laggies, S., Neumann, B., Seiffart, V., Lindenmaier, W., Gruber, AD., Ringe, J., Häupl, T., Thorey, F., Willbold, E., Corbeau, P., Gross, G.

Strategy for anti-aquaporin-4 auto-antibody identification and quantification using a new cell-based assay.

De Vidi I, Boursier G, Delouche N, Portalès P, Cadars E, Bouthier M, Mettling C, Lin YL, Thouvenot E, Carlander B, Camu W, Antel JP, Bar-Or A, Zephir H, Vermersch P, De Seze J, Corbeau P, Eliaou JF, Vincent T.

CXCR3 expression on peripheral CD4(+) T cells as a predictive marker of response to treatment in chronic hepatitis C.

Perney P, Turriere C, Portalès P, Rigole H, Psomas C, Blanc F, Clot J, Corbeau P.

CCR5 antagonism in HIV infection: ways, effects, and side effects

Corbeau, P., Reynes, J.

Peripheral blood T4 cell surface CCR5 density as a marker of activity in rheumatoid arthritis treated with anti-CD20 monoclonal antibody.

Portalès P, Fabre S, Vincent T, Desmetz C, Réant B, Noël D, Clot J, Jorgensen C, Corbeau P.

The chemokine CCL5 regulates the in vivo cel surface of its receptor, CCR5.

Lin, Y.L., Mettling, C., Portalès, P., Rouzier, R., Clot, J., Reynes, J., Corbeau, P.

Effective gene therapy in a mouse model of prion diseases

Toupet, K., Compan, V., Crozet, C., Mourton-Gilles, C., Mestre-Francés, N., Ibos, F., Corbeau, P., Verdier, JM., Perrier, V.

Galphai protein-dependant extracellular signal-regulated kinase-1/2 activation is required for HIV-1 reverse transcription

Mettling, C., Desmetz, C., Fiser, AL., Réant, B., Corbeau, P., Lin, YL.

Interfering RNA and HIV: reciprocal interferences

Corbeau P.

Cell surface CCR5 density determines the intensity of T cell migration towards rheumatoid arthritis synoviocytes

Desmetz C, Lin YL, Mettling C, Portales P, Noel D, Clot J, Jorgensen C, Corbeau P.

Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance

Bakkour, N., Lin, YL., Maire, S., Ayadi, L., Mahuteau-Betzer, F., Nguyen, C.H., Mettling, C., Portales, P. , Grierson, D., Chabot, B., Jeanteur, P., Branlant, C., Corbeau, P., Tazi, J.

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients

Petitjean, G., Al Tabaa, Y., Tuaillon, E., Mettling, C., Baillat, V., Reynes, J., Segondy, M., Vendrell, JP.

The efficiency of R5 HIV-1 infection is determined by CD4 T-cell surface CCR5 density through Galphai-protein signalling.

Lin, YL, Mettling, C., Portales, P., Reant, B., Robert-Hebmann, V., Reynes, J., Clot, J., Corbeau, P.

Chordin is under-expressed in ovarian tumors and reduces tumor cells motility.

Moll, F., C. Millet, D. Noël. B. Orsetti, A. Bardin, D. Katsaros, C. Jorgensen, M. Garcia, C. Theillet, P. Pujol and V. François.

Structure-based design, synthesis, and biological evaluation of novel inhibitors of human cyclophilin A.

Guichou JF, Viaud J, Mettling C, Subra G, Lin YL, Chavanieu A.

C-terminal processing of fibrillar procollagens is the only BMP-1-dependent activity to be enhanced by PCPE-1.

Moali, C., Font, B., Ruggiero, F., Eichenberger, D., Rousselle, P., François, V., Oldberg, A., Bruckner-Tuderman, L., Hulmes, D.J.

The immunological response to highly active antiretroviral therapy is linked to CD4+ T-cell surface CCR5 density.

Vincent T, Portales P, Baillat V, Eden A, Clot J, Reynes J, Corbeau P.

The strength of the chemotactic response to a CCR5 binding chemokine is determined by the level of cell surface CCR5 density.

Desmetz C, Lin YL, Mettling C, Portales P, Rabesandratana H, Clot J, Corbeau P.

The expression of cytotoxic mediators is altered in mononuclear cells of patients with melanoma and increased by interferon-alpha treatment.

Guillot, B., Portales, P., Thanh, AD., Merlet, S., Dereure, O., Clot, J., Corbeau, P.

T-cell surface CCR5 density is not correlated with hepatitis severity in hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic use of CCR5 antagonists.

Vincent, T., P. Portales, V. Baillat, C. Merle de Boever, V. Le Moing, M. Vidal, J. Ducos, J. Clot, J. Reynes, and P. Corbeau

Effects of virion surface gp120 density on infection by HIV-1 and viral production by infected cells

Bachrach, E., Dreja, H., Lin, Y.-L., Mettling, C., Pinet, V., Corbeau, P., Piechaczyk., M.

G protein signaling triggered by R5 Human Immunodeficiency Virus type 1 increases virus replication efficiency in primary lymphocytes

Lin, Y.-L., Mettling, C., Portales, P., Réant, B., Clot, J., Corbeau, P.

CXCR4 over-expression during the course of HIV-1 infection correlates with the emergence of X4 strains

Lin, Y.-L., Portalès, P., Segondy, M., Baillat, V., Merle de Boever, C., Le Moing, V., Réant, B., Montes, B., Clot, J., Reynes, J., Corbeau, P.

Deletion of epidermal growth factor-like domains converts mammalian tolloid into a chordinase and effective procollagen C-proteinase

Garrigue-Antar , L., Francois, V., Kadler, K.E.

Feline immunodeficiency virus vectors for efficient transduction of primary human synoviocytes: application to an original model of rheumatoid arthritis

Lin, Y.-L., Noel, D., Mettling, C., Réant, B., Clot, J., Jorgensen, C., Corbeau, P. Reynes J, Baillat V, Portales P, Clot J, Corbeau P.

Relationship between CCR5 density and viral load after discontinuation of antiretroviral therapy

Reynes, J., Baillat, V., Portalès, P., Clot, J., Corbeau, P.

Diminished CD4+ T cell surface CCR5 expression in alcoholic patients

Perney, P., P. Portalès, J. Clot, F. Blanc, and P. Corbeau

Vitamin E supplementation increases the expression of the CCR5 coreceptor in HIV-1 infected subjects

Portales, P., Guerrier, T., Mettling, C., Lin, Y.-L., Baillat, V., Merle de Boever, C., Le Moing, V.,Segondy, M., Tramoni, C., Clot, J., Reynes, J., Corbeau, P.

T-cell surface CCR5 density is not correlated with hepatitis severity in hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic use of CCR5 antagonists

Vincent, T., Portales, P., Baillat, V., Merle de Boever, C., Le Moing, V., Vidal, M., Ducos, J., Clot, J., Reynes, J., Corbeau, P.

Interferon-alpha restores HIV-induced alteration of natural killer cell perforin expression in vivo

Portales, P., Reynes, J., Pinet, V., Rouzier-Panis, R., Baillat, V., Clot, J., Corbeau, P.

Perforin expression in T cells and virological reponse to PEG-interferon alpha2b in HIV-1 infection

Portales, P., Reynes, J., Rouzier-Panis, R., Baillat, V., Clot, J., Corbeau, P

Cholesterol requirement of hepatitis B surface antigen (HBsAg) secretion

Lin, YL., Shiao, MS., Mettling, C. and Chou, CK

Low CD4+ T-cell surface CCR5 density as a cause of resistance to in vivo HIV-1 infection

Reynes, J., Baillat, V., Portalès, P., Clot, J., Corbeau, P.

Response to treatment and disease progression linked to CD4+ T cell surface CC Chemokine Receptor 5 density in Human Immunodeficiency Virus type 1 vertical infection

Gervaix A, Nicolas J, Portales P, Posfay-Barbe K, Wyler CA, Segondy M, Avinens O, Siegrist CA, Clot J, Eliaou JF, Astruc J, Corbeau P

Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection

Lin, Y.-L., Mettling, C., Portales, P., Reynes, J., Clot, J., Corbeau, P.

CD4 T cell surface CCR5 density as a host factor in HIV-1 disease progression

Reynes, J., Portales, P., Segondy, M., Baillat, V., André, P., Avinens, O., Picot, M.-C., Clot, J., Eliaou, J.-F., Corbeau, P.

Sex difference in HIV-1 load due to sex difference in CCR5 expression

Portales, P., Clot, J., Corbeau, P.

The human chordin gene encodes several differentially expressed spliced variants with distinct BMP opposing activities.

Millet, C., P. Lemaire, B. Orsetti, P. Guglielmi and V. François

T cell development and T cell responses in mice with mutations affecting tyrosines 292 or 315 of the ZAP-70 protein tyrosine kinase

Magnan A, Di Bartolo V, Mura AM, Boyer C, Richelme M, Lin YL, Roure A, Gillet A, Arrieumeriou C, Acuto O, Malissen B, Malissen M

CD4+ T cell surface CCR5 density and virus load in persons infected with Human Immunodeficiency Virus type 1

Reynes, J., Portales, P., Clot, J., Corbeau, P.

CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1

Reynes, J., Portales, P., Segondy, M., Baillat, V., André, P., Réant, B., Avinens, O., Couderc, G., Benkirane, M., Clot, J., Eliaou, J.F., Corbeau, P.

Complexes Formation between Insulin Receptor and Extracellular Signal-Regulated Kinase ERKs

Yea-Lih Lin, Clément Mettling and Chen-Kung Chou

Rap1 Suppressed Tumorigenesis Is Concomitant with the Interference in Ras Effector Signaling

Lin, Y-L., Mettling, C., Chou, C-K.

A new family of histone deacetylases related to Saccharomyces Cerevisae HDA1p.

Fischle, W., Emiliani, S., Hendzel, M.J., Nagase, T., Nomura, N., Voelter, W. and Verdin, E.

Genomic organization and chromosomal localization of the human histone deacetylase 3 gene.

Mahlknecht, U., Emiliani, S., Najfeld, V., Young, S. and Verdin, E.

Acetylation of the HIV-1 tat protein by p300 is important for its transcriptional activity.

Ott, M., Schnolzer, M., Garnica, J., Fischle, W., Emiliani, S., Rackwitz, H-R., Verdin, E.

Anti-HIV effects of HIV vectors.

Corbeau, P. and Wong-Staal, F.

Transduction of human macrophages using a stable HIV-1/HIV-2-derived gene delivery system.

Corbeau, P., Kraus, G. and Wong-Staal, F.

Mutations in the tat gene are responsible for human immunodeficiency virus type 1 postintegration latency in the U1 cell line.

Emiliani, S., Fischle, W., Ott, M., Van Lint, C., Amella, C.A. and Verdin, E.

Characterization of a new human RPD3 ortholog HDAC3.

Emiliani, S., Fischle, W., Van Lint, C., Al-Abed, Y. and Verdin, E.

Hybrid polard compounds selected as inducers of differentiation of transformed cells inhibit histone deacetylase activity.

Richon, V.M., Emiliani, S., Verdin, E., Ngo, L., Webb, Y., Breslow, R., Rifking, R.A. and Marks, P.A.

Phosphatidylinositol 3-Kinase Is Required for the Regulation of Hepatitis B Surface Antigen Production and Mitogen-Activated Protein Kinase Activation by Insulin but Not by TPA

Yea-Lih Lin and Chen-Kung Chou

PUBLICATIONS COMMUNES

PABPN1 shuts down alternative poly(A) sites

Simonelig, M
2012 - Cell Res. , 22, 10, 1419-1421. doi: 10.1038/cr.2012.86 22641371
Service porteur : mRNA Regulation and Development

Physiological suppression of microRNA-silencing pathway by HIV-1 during virus replication

Triboulet, Robinson., Bernard Mari, Yea-Lih Lin, Christine Chable-Bessia, Yamina Bennasser, Kevin Lebrigand, Bruno Cardinaud, Thomas Maurin, Pascal Barbry, Vincent Baillat, Jacques Reynes, Pierre Corbeau, Kuan-Teh Jeang and Monsef Benkirane.
2007 - Science , 315, 5818, 1579-1582. 17322031
Service porteur : Laboratory of Molecular Virology

Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation

Malki, S., Nef, S., Notarnicola, C., Thevenet, L., Gasca, S., Méjean, C., Berta, P., Poulat, F., Boizet-Bonhoure, B.
2005 - EMBO J , 24(10):1798-809 15889150
Service porteur : Development and Pathology of the gonad

GUIGUES Adeline
GUIGUES Adeline

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YOUNAS Mehwish
YOUNAS Mehwish
Research associate at University of Manchester

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BOULOUIS Caroline
BOULOUIS Caroline

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PSOMAS Katerina-Christina
PSOMAS Katerina-Christina
Spécialiste en médecine interne

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VIALA Benjamin
VIALA Benjamin
PHc en maladies infectieuses chez Centre Hospitalier Alpes Léman

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DESIGAUD Delphine
DESIGAUD Delphine

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RENAUD Elea
RENAUD Elea
UFR médecine

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REANT Brigitte
REANT Brigitte
Retraitée

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FISER Anne-laure
FISER Anne-laure

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DE VIDI Isabelle
DE VIDI Isabelle

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GASCA Stephan
GASCA Stephan

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MILITELLO Muriel
MILITELLO Muriel
CRBM

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TONG Xiao
TONG Xiao

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GUGLIELMI Laurence
GUGLIELMI Laurence

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GRANDE Emilie
GRANDE Emilie

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DUQUENNE Charline
DUQUENNE Charline
Chef de projets R&D Développement Immunoessais chez Thermo Fisher Scientific

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CAMPOS Mauricio
CAMPOS Mauricio
IRMB, Inserm

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FERRARIS Pauline
FERRARIS Pauline
Chef de projet Recherche & Développement IVD

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Topic: Immune activation as a cause of insulin resistance and metabolic syndrome in adults living with HIV-1 on effective antiretroviral therapy
Lucy Kundura 
October 2017-October 2021

Pierre CORBEAU, MD and PhD, Professor of Medicine

Pierre CORBEAU performed his medical internship at the University Hospitals of Montpellier and Marseille in Cancerology, Infectious Diseases, Rheumatology and Immunology.
 

He was Assistant Hospitalier-Universitaire and Maître de Conférence des Universités-Praticien Hospitalier at the University
Hospital of Montpellier. He is currently Professeur des Universités-Praticien Hospitalier and Head of the Immunology Department at the University Hospital of Nîmes.
He got his Master degree and worked for his PhD at the Marseille-Luminy Center for Immunology. He had postdoctoral scholarships at the Pasteur Institute, at the Institute of Cancer Research, University of London, UK, and at the University of California, San Diego, USA. He is currently Head of a Research Group at the Institute for Human Genetics, UMR9002, at Montpellier.
He has taught in various Universities in France, for the Canadian Mentorat on HIV and at the University of California, San Diego, USA.
He has worked as an MD and a researcher from the beginning on HIV infection.