Virologie Moléculaire

Bases moléculaires de pathologies humaines

Nos projets de recherche s’inscrivent dans une thématique visant à mieux comprendre les interactions entre le VIH et la cellule hôte. Pour cela, nous cherchons à identifier et à étudier la régulation de l’activité des facteurs cellulaires impliqués dans l’activation et la répression de la réplication virale. Nous nous intéressons plus particulièrement à la régulation de l’expression des gènes viraux. En effet, chez les patients infectés par le VIH, le taux de réplication virale, contrôlé en partie par la transcription du génome viral, est un facteur critique, déterminant la progression de la maladie vers le stade SIDA.

La transcription des gènes du VIH est sous le contrôle du transactivateur viral Tat et des facteurs de transcription cellulaires qui interagissent avec sa région promotrice LTR 5’ (“Long Terminal Repeat”). Les déterminants cellulaires impliqués dans la latence transcriptionnelle du VIH, phénomène à l’origine de l’établissement du réservoir viral observé chez les patients infectés, sont mal connus.

Ce réservoir viral, constitué principalement de cellules lymphocytaires T CD4+ mémoires infectées mais non productrices de virus, est un des obstacles majeurs responsables de l’échec des thérapies anti-VIH. Ces cellules stables sont insensibles aux traitements et invisibles pour le système immunitaire. La réactivation du virus dans ces cellules permettra de les rendre accessibles aux traitements anti-viraux. La combinaison d’agents activateurs du virus dans les cellules réservoirs et la tri-thérapie (HAART) permettront de « purger » le réservoir viral et par conséquent, éliminer le virus.

Plusieurs études montrent un rôle important de la structure chromatinienne dans le choix des sites d’intégration et la régulation de la transcription à partir du promoteur viral. De plus, des études récentes suggèrent une interaction physique et fonctionnelle entre le VIH et la machinerie RNAi cellulaire. Afin d’étudier le rôle de la chromatine et de la machinerie RNAi cellulaire dans la réplication du VIH, nous appliquons plusieurs techniques incluant une approche protéomique pour identifier les facteurs cellulaires impliqués dans l’activation et la répression du LTR. Le recrutement de ces facteurs au niveau du LTR est analysé par immunoprécipitation de chromatine et PCR quantitative et par immunofluoresence.

Monsef BENKIRANE
Chercheur

0434359996
Benjamin Descours
Benjamin DESCOURS
Chercheur

0434359988
Joao Rodrigo DIOGO DIAS
Joao Rodrigo DIOGO DIAS
Chercheur

0434359988
Christine Neuveut
Christine NEUVEUT
Chercheur

0434359988
Bijan SOBHIAN
Chercheur

0434359976
Scarlette Abbou
Scarlette ABBOU
IT

0434359976
Lucie Bonnet-Madin
Lucie BONNET-MADIN
IT

0434359976
Gael Petitjean
Gael PETITJEAN
IT

0434359988
Suzie Houssier
Suzie HOUSSIER
Postdoc

0434359988
Nazim Sarica
Nazim SARICA
Postdoc

0434359988
Cyprien Jahan
Cyprien JAHAN
Doctorant

0434359976
Basile Jay
Basile JAY
Doctorant

0434359988

PUBLICATIONS DE L'ÉQUIPE

RNF219 regulates CCR4-NOT function in mRNA translation and deadenylation

Aude Guénolé, Fabien Velilla, Aymeric Chartier, April Rich, Anne-Ruxandra Carvunis, Claude Sardet, Martine Simonelig & Bijan Sobhian

+ Régulation des ARNm et Développement

en savoir plus

Exploring histone loading on HIV DNA reveals a dynamic nucleosome positioning between unintegrated and integrated viral genome.

Machida S, Depierre D, Chen HC, Thenin-Houssier S, Petitjean G, Doyen CM, Takaku M, Cuvier O, Benkirane M

en savoir plus

FTSJ3 is an RNA 2'-O-methyltransferase recruited by HIV to avoid innate immune sensing.

Ringeard M, Marchand V, Decroly E, Motorin Y, Bennasser Y

Posttranscriptional Regulation of HIV-1 Gene Expression during Replication and Reactivation from Latency by Nuclear Matrix Protein MATR3.

Sarracino A, Gharu L, Kula A, Pasternak AO, Avettand-Fenoel V, Rouzioux C, Bardina M, De Wit S, Benkirane M, Berkhout B, Van Lint C, Marcello A

Descours et al. reply.

Descours B, Petitjean G, Benkirane M

XPC is an RNA polymerase II cofactor recruiting ATAC to promoters by interacting with E2F1.

Bidon B, Iltis I, Semer M, Nagy Z, Larnicol A, Cribier A, Benkirane M, Coin F, Egly JM, Le May N

CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses

Descours B, Petitjean G, López-Zaragoza JL, Bruel T, Raffel R, Psomas C, Reynes J, Lacabaratz C, Levy Y, Schwartz O, Lelievre JD, Benkirane M.

HEXIM1 and NEAT1 lncRNA form a multi subunit complex that regulates DNA-mediated innate immune response

Morchikh, M., Cribier, A., Raffel, R., Amraoui, S., Cau, J., Severac, D., Dubois, E., Schwartz, O., Bennasser, Y., Benkirane, M.

Upregulated LINE-1 Activity in the Fanconi Anemia Cancer Susceptibility Syndrome Leads to Spontaneous Pro-inflammatory Cytokine Production

Bregnard, C, Guerra, J, Dejardin, S, Passalacqua, F, Benkirane, M, Laguette, N


+ Bases Moléculaires de l’Inflammation

Dasatinib Inhibits HIV-1 Replication through the Interference of SAMHD1 Phosphorylation in CD4+ T Cells

Bermejo M, López-Huertas MR, García-Pérez J, Climent N, Descours B, Ambrosioni J, Mateos E, Rodríguez-Mora S, Rus-Bercial L, Benkirane M, Miró JM, Plana M, Alcamí J, Coiras M.

IL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cycle

Coiras M, Bermejo M, Descours B, Mateos E, García-Pérez J, López-Huertas MR, Lederman MM, Benkirane M, Alcamí J.

International AIDS Society global scientific strategy: towards an HIV cure 2016

Deeks SG, Lewin SR, Ross AL, Ananworanich J, Benkirane M, Cannon P, Chomont N, Douek D, Lifson JD, Lo YR, Kuritzkes D, Margolis D, Mellors J, Persaud D, Tucker JD, Barre-Sinoussi F; International AIDS Society Towards a Cure Working Group, Alter G, Auerbach J, Autran B, Barouch DH, Behrens G, Cavazzana M, Chen Z, Cohen ÉA, Corbelli GM, Eholié S, Eyal N, Fidler S, Garcia L, Grossman C, Henderson G, Henrich TJ, Jefferys R, Kiem HP, McCune J, Moodley K, Newman PA, Nijhuis M, Nsubuga MS, Ott M, Palmer S, Richman D, Saez-Cirion A, Sharp M, Siliciano J, Silvestri G, Singh J, Spire B, Taylor J, Tolstrup M, Valente S, van Lunzen J, Walensky R, Wilson I, Zack J.

Phosphorylation of murine SAMHD1 regulates its antiretroviral activity

Wittmann S, Behrendt R, Eissmann K, Volkmann B, Thomas D, Ebert T, Cribier A, Benkirane M, Hornung V, Bouzas NF, Gramberg T.

Towards an HBV cure: state-of-the-art and unresolved questions-report of the ANRS workshop on HBV cure

Zeisel MB, Lucifora J, Mason WS, Sureau C, Beck J, Levrero M, Kann M, Knolle PA, Benkirane M, Durantel D, Michel ML, Autran B, Cosset FL, Strick-Marchand H, Trépo C, Kao JH, Carrat F, Lacombe K, Schinazi RF, Barré-Sinoussi F, Delfraissy JF, Zoulim F.

A Testis-Specific Chaperone and the Chromatin Remodeler ISWI Mediate Repackaging of the Paternal Genome

Doyen CM1, Chalkley GE1, Voets O1, Bezstarosti K2, Demmers JA2, Moshkin YM1, Verrijzer CP3.

+ Méiose et recombinaison

SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage

Clifford R, Louis T, Robbe P, Ackroyd S, Burns A, Timbs AT, Colopy GW, Dreau H, Sigaux F, Judde JG, Rotger M, Telenti A, Lin YL, Pasero P, Maelfait J, Titsias M, Cohen DR, Henderson SJ, Ross M, Bentley D, Hillmen P, Pettitt A, Rehwinkel J, Knight SJ, Taylor JC, Crow YJ, Benkirane M, Schuh A.

+ Maintien de l'intégrité du génome au cours de la réplication

The Tudor Domain Protein Spindlin1 Is Involved in Intrinsic Antiviral Defense against Incoming Hepatitis B Virus and Herpes Simplex Virus Type 1

Ducroux A, Benhenda S, Rivière L, Semmes OJ, Benkirane M, Neuveut C.

Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes

Stadelmayer B, Micas G, Gamot A, Martin P, Malirat N, Koval S, Raffel R, Sobhian B, Severac D, Rialle S, Parrinello H, Cuvier O, Benkirane M

Identification of histone 3 variant 2 interacting factors

Latreille D, Bluy L, Benkirane M, Kiernan RE.


+ Régulation des gènes

Premature termination of transcription by RNAP II: The beginning of the end.

Contreras X, Benkirane M, Kiernan R.


+ Régulation des gènes

The PRMT1 methyltransferase is a binding partner of HBx and a negative regulator of hepatitis B virus transcription

Benhenda, S., Ducroux, A., Rivière, L., Sobhian, B., Ward, M., Dion, S., Hantz, O., Protzer, U., Michel, ML., Benkirane, M., Semmes, OJ., Buendia, MA., Neuveut, C.

Monsef Benkirane awarded 2013 Ming K. Jeang Foundation Retrovirology Prize: Landmark HIV-1 research honoured

Berkhout B, Lever A, Wainberg M, Fassati A, Borrow P, Fujii M

Phosphorylation of SAMHD1 by CyclinA2/CDK1 regulates its restriction activity towards HIV-1

Cribier, A., Descours, B., Chaves Valadeo, AL., Laguette, N., Benkirane , M.

SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates

Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, Bloch N, Maudet C, Bertrand M, Gramberg T, Pancino G, Priet S, Canard B, Laguette N, Benkirane M, Transy C, Landau NR, Kim B, Margottin-Goguet F.

Hyperthermia Stimulates HIV-1 Replication

Roesch F, Meziane O, Kula A, Nisole S, Porrot F, Anderson I, Mammano F, Fassati A, Marcello A, Benkirane M, Schwartz O

Towards an HIV cure: a global scientific strategy

The International AIDS Society Scientific Working Group on HIV Cure, Deeks SG, Autran B, Berkhout B, Benkirane M, Cairns S, Chomont N, Chun TW, Churchill M, Mascio MD, Katlama C, Lafeuillade A, Landay A, Lederman M, Lewin SR, Maldarelli F, Margolis D, Markowitz M, Martinez-Picado J, Mullins JI, Mellors J, Moreno S, O'Doherty U, Palmer S, Penicaud MC, Peterlin M, Poli G, Routy JP, Rouzioux C, Silvestri G, Stevenson M, Telenti A, Lint CV, Verdin E, Woolfrey A, Zaia J, Barré-Sinoussi F.

Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac

Brandariz-Nuñez A, Valle-Casuso JC, White TE, Laguette N, Benkirane M, Brojatsch J, Diaz-Griffero F

SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates

Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, Bloch N, Maudet C, Bertrand M, Gramberg T, Pancino G, Priet S, Canard B, Laguette N, Benkirane M, Transy C, Landau NR, Kim B, Margottin-Goguet F.

Evolutionary and Functional Analyses of the Interaction between the Myeloid Restriction Factor SAMHD1 and the Lentiviral Vpx Protein

Laguette N, Rahm N, Sobhian B, Chable-Bessia C, Münch J, Snoeck, Sauter D, Switzer WM, Heneine W, Kirchhoff F, Delsuc F, Telenti A and Benkirane M.

SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+ T-cells

Descours B, Cribier A, Chable-Bessia C, Ayinde D, Rice G, Crow Y, Yatim A, Schawartz O, Laguette N, Benkirane M.

NOTCH1 Nuclear Interactome Reveals Key Regulators of Its Transcriptional Activity and Oncogenic Function

Yatim, A., Benne, C., Sobhian, B., Laurent-Chabalier, S., Deas, O., Judde, JG., Lelievre, JD., Levy, Y., Benkirane, M.

Microprocessor, Setx, Xrn2 and Rrp6 Co-Operate to Induce Premature Termination of Transcription by RNAPII

Wagschal, A., Rousset, E., Basavarajaiah, P., Contreras, X. , Harwig, A., Laurent-Chabalier, S. , Nakamura, M., Chen, X., Zhang, K., Meziane, O., Boyer, F., Parrinello, H., Berkhout, B., Terzian, C., Benkirane, M., Kiernan, R.


+ Régulation des gènes

How Samhd1 changes our view of viral restriction

Laguette N, Benkirane M.

Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin

He, N., Chan, CK., Sobhian, B., Chou, S., Xue, Y., Liu, M., Alber, T., Benkirane, M., Zhou, Q

Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features.

Cayrou C, Coulombe P, Vigneron A, Stanojcic S, Ganier O, Peiffer I, Rivals E, Puy A, Laurent-Chabalier S, Desprat R, Méchali M.


+ Réplication et Dynamique du Génome

Competition for XPO5 binding between Dicer mRNA, pre-miRNA and viral RNA regulates human Dicer levels

Bennasser, Y., Chable-Bessia, C., Triboulet, R., Gibbings, D., Gwizdek, C., Dargemont, C., Kremer, EJ., Voinnet, O., Benkirane, M.

SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx.

Laguette, N., Sobhian, B., Casartelli, N., Ringeard, M., Chable-Bessia, C., Ségéral, E., Emiliani, S., Schwartz, O., Benkirane, M

Epidemiology of HIV infection in the Middle East and North Africa

Abu-Raddad, LJ., Hilmi, N., Mumtaz, G., Benkirane, M., Akala, FA., Riedner, G., Tawil, O., Wilson, D.

HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP

Sobhian, B., Laguette, N., Yatim, A., Nakamura, M., Levy, Y., Kiernan, R., Benkirane, M.

+ Régulation des gènes

Lessons from interconnected ubiquitylation and acetylation of p53: think metastable networks

Benkirane, M., Sardet, C, Coux,O.

Endogenous Retroviruses: Thierry Heidmann wins the 2009 Retrovirology prize.

Saib, A., Benkirane, M.

Suppression of HIV-1 replication by microRNA effectors

Chable-Bessia, C., Meziane, O., Latreille, D., Triboulet, R., Zamborlini, A., Wagschal, A., Jacquet, JM., Reynes, J., Levy, Y., Saib, A., Bennasser, Y., Benkirane, M.

Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post integration latency.

du Chéné, I., Basyuk, E., Lin,YL., Triboulet, R., Knezevich, A., Chable-Bessia, C., Mettling, C., Baillat, V., Reynes, J., Corbeau, P., Bertrand, E., Marcello, A., Emiliani, S., Kiernan, R., Benkirane, M.

+ Régulation des gènes

Intrinsic ubiquitylation activity of PCAF controls the stability of the oncoprotein Hdm2

Linares, Laetitia, Rosemary Kiernan, Robinson Triboulet, Christine Chable-Bessia, Daniel Latreille, Olivier Cuvier, Matthieu Lacroix, Laurent Le Cam, Olivier Coux, and Monsef Benkirane.

+ Régulation des gènes

The Proteasome Regulates HIV-1 Transcription by Both Proteolytic and Non-Proteolytic Mechanisms

Lassot, L., Latreille, D., Rousset, E., Sourisseau, M., Linares, L.K., Chable-Bessia, C., Coux, O., Benkirane, M., Kiernan, R.

+ Régulation des gènes

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.

+ Domiciliation, activation immunitaire et infection

Interplay between HIV-1 replication and the microRNA-silencing pathway.

Triboulet, R., Benkirane, M.

Small non-coding RNAs, mammalian cells, and viruses: regulatory interactions?

Yeung, ML., Benkirane, M., Jeang, KT.

The HIV-1 Tat protein stimulates reverse transcription in vitro.

Apolloni, A., Meredith, LW., Suhrbier, A., Kiernan, R., Harrich, D

+ Régulation des gènes

PPAR{gamma} Recruits the P-TEFb Complex to Activate Transcription and Promote Adipogenesis.

Iankova I, Petersen RK, Annicotte JS, Chavey C, Hansen JB, Kratchmarova I, Sarruf D, Benkirane M, Kristiansen K, Fajas L.

Requirement for SWI/SNF chromatin-remodeling complex in Tat-mediated activation of the HIV-1 promoter.

Treand C, du Chene I, Bres V, Kiernan R, Benarous R, Benkirane M, Emiliani S.

+ Régulation des gènes

ERK5 Activates NF-{kappa}B in Leukemic T Cells and Is Essential for Their Growth In Vivo.

Garaude J, Cherni S, Kaminski S, Delepine E, Chable-Bessia C, Benkirane M, Borges J, Pandiella A, Iniguez MA, Fresno M, Hipskind RA, Villalba M.

Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing

Bennasser Y, Le SY, Benkirane M, Jeang KT

HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses

Col E, Caron C, Chable-Bessia C, Legube G, Gazzeri S, Komatsu Y, Yoshida M, Benkirane M, Trouche D, and Khochbin S

p300 modulates ATF4 stability and transcriptional activity independently of its acetyltransferase domain.

Lassot I, Estrabaud E, Emiliani S, Benkirane M, Benarous R, Margottin-Goguet F.

Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1.

Espert L, Degols G, Lin YL, Vincent T, Benkirane M, Mechti N.

Regulation of human SRY subcellular distribution by its acetylation/deacetylation

Thevenet L, Mejean C, Moniot B, Bonneaud N, Galeotti N, Aldrian-Herrada G, Poulat F, Berta P, Benkirane M, Boizet-Bonhoure B

Simian Virus 40-Based Replication of Catalytically Inactive Human Immunodeficiency Virus Type 1 Integrase Mutants in Nonpermissive T Cells and Monocyte-Derived Macrophages

Richard Lu, Noriko Nakajima, Wolfgang Hofmann, Monsef Benkirane, Kuan Teh-Jeang, Joseph Sodroski, and Alan Engelman

Ubiquitination of human T-cell leukemia virus type 1 tax modulates its activity

Peloponese JM Jr, Iha H, Yedavalli VR, Miyazato A, Li Y, Haller K, Benkirane M, Jeang KT

Regulation of human SRY subcellular distribution by its acetylation/deacetylation.

Thevenet, L., Mejean, C., Moniot, B., Bonneaud, N., Galeotti, N., Aldrian-Herrada, G., Poulat, F., Berta, P., Benkirane, M., Boizet-Bonhoure, B.


+ Développement et Pathologie de la Gonade

Post-activation turn-off of NF-kB-dependent transcription is regulated by acetylation of p65

Rosemary E. Kiernan, Vanessa Bres, Raymond W.M. Ng, Marie-Pierre Coudart, Selma El Messaoudi, Claude Sardet, Dong-Yan Jin, Stephane Emiliani, and Monsef Benkirane

A non proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter

Vanessa Brès, Rosemary E. Kiernan, Laetitia K. Linares, Christine Chable-Bessia, Olga Plechakova, Céline Tréand, Stephane Emiliani, Jean-Marie Peloponese, Kuan-Teh Jeang, Olivier Coux, Martin Scheffner, and Monsef Benkirane

+ Régulation des gènes

Tat and TAR RNA independent induction of HIV-1 LTR by Human and Murine cyclin T1 requires Sp1

Venkat S.R.K. Yedavalli, Monsef Benkirane, and Kuan Teh Jeang

Tat acetyl-acceptor lysines are important for Human Immunodeficiency Virus type-1 replication

Brès, V., Rosemary Kiernan, Stéphane Emiliani and Monsef Benkirane

+ Régulation des gènes

Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF.

Brès V. Tagami H. Péloponèse J.M. Loret E. Jeang K-T. Nakatani Y. Emiliani S. Benkirane M. and Kiernan ER.

+ Régulation des gènes

Interaction between cyclin T1 and SCFSKP2 targets CDK9 for ubiquitination and degradation by the proteasome.

Kiernan, R., Emiliani, S., Nakayama, K., Castro, A., Labbé, J.C., Lorca, T., Nakayama, K.-I., and Benkirane, M.

+ Régulation des gènes

Tat Protein of Human Immunodeficiency Virus Type 1 Induces Interleukin-10 in Human Peripheral Blood Monocytes: Implication of Protein Kinase C-Dependent Pathway

Badou A, Bennasser Y, Moreau M, Leclerc C, Benkirane M, Bahraoui E

Selective CXCR4-antagonism by Tat:Implications for in vivo expansion of co-receptor use by HIV-1

Xiao, H., Neuveut, C., Tiffany, H.L., Murphy, P.M, Benkirane, M., Rich, E.A., and Jeang, K.-T.

HIV-1 Tat transcriptional activity is regulated by acetylation.

Kiernan, R., Vanhulle, C., Schiltz, L., Adam, E., Xiao, H., Maudoux, F., Calomme, C., Burny, A., Nakatani, Y., Jeang, K.-T., Benkirane, M. and Van Lint, C.

+ Régulation des gènes

Activation of integrated provirus requires histone acetyltransferase. p300 and P/CAF are coactivators for HIV-1 Tat.

Benkirane, M., Chun, R.F., Xiao, H., Ogryzko, V.V., Howard, B.H., Nakatani, Y. and Jeang, K.-T..

Interaction of the second coding exonof Tat withhuman EF-1 delta delineates a mechanism forHIV-1 shut-off of host mRNA translation.

Xiao, H., Neuveut, C., Benkirane, M. and K.T., J.

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DOYEN Cécile
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GAYRAUD Thomas
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YATIM Ahmad
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AP-HP
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BARCKMANN Bridlin
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CHU de Montpellier
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KANWAL Shahzina
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Sujet: analyse du contexte chromatinnien et tridimensionnel des sites d'intégrations du VIH chez des patients sous traitement
Thésard: Raoul Raffel sous la direction de Monsef Benkirane
En préparation depuis le 15-10-2015

Thèses soutenues