CONTACT

Head of the team

Fabien Zoulim

fabien.zoulim@inserm.fr

+33 (0)4 72 68 19 70 (assistant)

Inserm building
151 Cours Albert Thomas
69003 Lyon
France
ZOULIM Fabien
Professeur des Universités - Praticien Hospitalier (UCLB - HCL)
BARTOSCH Birke
DURANTEL David
PARENT Romain
MICHELET Maud
Ingénieur d'étude Inserm
maud.michelet@inserm.fr
FRESQUET Judith
Ingénieur d'études Inserm
judith.fresquet@inserm.fr
JAMARD Catherine
Technicienne Inserm
catherine.jamard@inserm.fr
MOLLE Jennifer

Assistante Ingénieure
jennifer.molle@inserm.fr

LUCIFORA Julie
STADELMAYER Bernd
Chercheur post-doctorant
marie-laure.plissonnier@inserm.fr
TESTONI Barbara
DIMIER Laura
FARHAT Rayan

Post-doctorant
rayan.farhat@inserm.fr

MAADADI Sarah
CHABROLLES Hélène

Etudiante en thèse
helene.chabrol@inserm.fr

LOCATELLI Maëlle
PECHEUR Eve-Isabelle
GRIGOROV Boyan

Maître de Conférences / U. de Lyon
boyan.grigorov@inserm.fr

REUNGOAT Emma
DIEDERICHS Audrey
CHARDES Brieux
INSCHAUSPE Aurore
CHAPUS Fleur
MONNIER Léa
FAURE-DUPUY Suzanne
BARNAULT Romain
FOCA Adrien
AILLOT Ludovic
COMBET Christophe
LAHLALI Thomas
SCHOLTES Caroline

Maître de conferences U. de Lyon
caroline.scholtes@inserm.fr

QUINET Jonathan
VEGNA Serena
DUPONCHEL Sarah
Salvetti Anna
MARTINEZ Guadalupe
Voir les objectifs et projets Voir les publications

OBJECTIVES

Hepatitis B and C viruses determine chronic infections of the liver in about 600 million people worldwide, and foster hepatic injuries such as steatosis and fibrosis that can lead to cirrhosis and hepatocarcinoma (HCC). The team's main aims consist in a better understanding of molecular mechanisms that allow establishment and maintenance of HBV and HCV infections, in the hope of developing novel antiviral strategies (either directly targeting the virus or through modulation of immune functions modulation). Our global purpose is to contribute to the eradication of hepatic viral infections, the prevention of liver cancer and the regression of its precursor pathologies such as fibrosis and cirrhosis.

B. TESTONI & F. ZOULIM GROUP

Biology of cccDNA and novel biomarkers for in chronic HBV infections

 

Context: The goals of current HBV therapy are to prevent the development of cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC) and death from HBV-related liver disease, which represents the 3rd mortality cause worldwide. This, associated to suboptimal vaccination coverage in highly endemic areas, make CHB a worldwide major health burden, with more than 240 million people being chronic carriers of the infection.

Current first-choice treatments for chronic hepatitis B (CHB) are able to efficiently induce viral suppression in the majority of patients, but life-long therapy is needed to maintain infection under control due to their inability to eliminate the virus from infected hepatocytes. Indeed, the hepatitis B virus (HBV) minichromosome, the so-called covalently closed circular (ccc)DNA, is wrapped around nucleosomes to form a stable, chromatinized structure that is regulated by epigenetic mechanisms and is responsible for viral persistence in the nucleus of infected cells. Moreover, the ability of HBV to integrate into the host genome hampers a complete sterilizing cure.

The residual viral replication and antigen production in most patients under treatment substantially contributes to the residual risk of hepatocarcinogenesis.

New therapeutic approaches are needed to overcome HBV persistence in the infected cells, or at least, to control its transcriptional and replicative activity.

Concomitantly, the advent of new combinatorial therapies requires the need of defining new endpoints for the assessment of therapeutic efficiency and of serum standardized assays representing surrogate markers intrahepatic viral activity.

 

Objectives:

1°) Generate new knowledge on cccDNA biology, in particular on the key steps leading to its formation and to its transcriptional regulation once the pool is established, in vitro and in vivo

2°) Investigate Gene editing approaches to induce cccDNA degradation

3°) Investigate new serum surrogate markers for intrahepatic cccDNA amount and/or activity; assess their correlation with intrahepatic HBV activity and evaluate their prognostic value in CHB patients cohorts

4°) Investigate the impact of viral/host genome genetic variability on cccDNA epigenetic regulation and on new antiviral treatments efficiency

5°) Analyze HBV integration in the host genome and its role in liver pathogenesis

A. SALVETTI, J. LUCIFORA, D. DURANTEL GROUP

HBV/HDV & intrinsic/innate immunity responses: from understanding to direct or “host-targeting” antiviral development

According to WHO, around 250 million individuals are chronically infected by hepatitis B virus (HBV) and have higher risk of developing severe liver diseases, such as fibrosis/cirrhosis, liver failure, hepatocellular carcinoma, which can lead to death. HBV circulates outside cells as an enveloped virus containing a relaxed circular partially dsDNA (rcDNA) as genetic material packaged within an icosahedral capsid. Besides playing an essential role in the formation of nucleocapsids and subsequent virions, the HBV core protein (HBc) is also located in the nucleus of infected cells where it has regulatory functions. Current clinically accepted antiviral treatments generally lead to a transient or long-lasting reduction of viremia in the blood of patients. However, the liver viral clearance is rarely obtained since the viral episome (cccDNA) persists in the nucleus of infected cells. Understanding the mechanisms responsible for viral establishment and persistent infections constitutes a major goal toward the development of new innovative therapies.

Around 15-20 million of people are chronically infected with both HBV and hepatitis Delta viruses (HDV). This co-infection is one of the most prevalent worldwide and lead to the most aggressive chronic form of viral hepatitis, with an accelerated progression towards fibrosis/cirrhosis and an increased risk of liver failure, liver cancer and death. Management of chronic hepatitis delta remains mostly empiric since there are currently no specific treatments. Pegylated interferon alpha, the only regimen recommended by international guidelines, is not well tolerated and can suppress HDV viremia in less than half of the treated patients but relapses after arrest of treatment are very often reported. The number of investigational drugs remains limited mainly because HDV can hardly be directly targeted since it highly depends on the cellular machinery for its replication.


Using original and relevant systems such as primary liver cells, 3D cultures, as well as mouse models, our research programs aim at generating knowledges on the life-threatening HBV and HDV (co-)infections in order to develop innovative therapeutic strategies, including immune therapeutics. The specific aims of the group are to:

1°) Determine the role of liver non-parenchymal cells in the establishment and maintenance of HBV/HDV (co)infections.

2°) Analyze the early hepatic intrinsic responses against incoming viral genomes in the nucleus. In particular our studies aim at characterizing the early DNA damage response (DDR) induced by the release of the HBV rcDNA in the nucleus and its impact on cccDNA formation.

3°) Identify HBc nuclear regulatory functions and its impact on the regulation of intrinsic cell responses Our approach relies on the proteomic identification of HBc interacting partners in the hepatocyte nucleus.

4°) Identify host (i.e. innate sensors) and viral factors influencing HBV/HDV infections outcome and response to IFN alpha treatment.

5°) Understand how HDV super-infection accelerate and increase the liver diseases originally caused by HBV persistence

6°) Test and develop innovative therapeutic strategies based on either the use of PRR agonists, the targeting of HBc with specific inhibitors (i.e., DAA), or the targeting of host-factors (i.e., HTA) required for both HBV and HDV replications.

 

Staff: 3 tenured researchers, 1 tenured Engineer (IE INSERM), 1 AI (CDD), 4 Post-docs, 6 PhD students;

Fundings: ANRS, FINOVI, Infect-ERA, Janssen, Gilead, Novira Pharma., Arbutus Biopharma, Roche, Assembly Biosciences;

Recent publications: 1. Diab et al., Hepatology, 2017; 2. Alfaiate et al., Antiviral Res. 2016; 3. Durantel et al., J Hepatol. 2016 ; 4. Lucifora et al., J Hepatol. 2016 ;  5. Zannetti et al., J Immunol. 2016; 6. Isorce et al., Antiviral Res. 2016; 7. Luangsay et al., J Hepatol. 2015a; 8. Luangsay et al., J Hepatol. 2015b; 9. Lucifora et al., Science. 2014 ; 10. Jammart et al., J Virol. 2013.  

B. BARTOSCH GROUP

Tumor cell-like metabolic adaptations in the pathophysiology of chronic viral hepatitis

Chronic infection with hepatitis B and C and D viruses (HBV/ HCV/HDV) is one of the main etiologies of hepatocellular carcinoma (HCC), the most common form of liver cancer. A major feature of chronic viral hepatitis is the frequent occurrence of oxidative stress and metabolic alterations, which play a major role in liver fibrosis and disease progression towards liver cancer.  At the interface between virology, cell biology and biochemistry, our laboratory is analyzing metabolic alterations and associated intracellular oxidative stress induced by hepatitis viruses and their respective roles in the development of liver fibrosis. We have found for example evidence for the installation of a tumor cell-like metabolism in HCV-infected cells, characterized by a special dependence on glutamine utilization. Importantly, altered glutamine fluxes impact mitochondria and mitochondrial functions and may alter cellular resistance to apoptosis, inflammatory processes, metabolic and redox homeostasis in infected cells and is thus potentially strongly pro-carcinogenic.

Our particular aims are:

·      To  show how hepatitis viruses modulate metabolic fluxes using biochemistry, molecular biology and metabolomics

·      To investigate how hepatitis viruses impact and alter mitochondrial structure and functions, via direct binding to these organelles or by altered function of mitochondrial or metabolic enzymes

·      Investigate how hepatitis virus-induced metabolic changes are linked to increased oxidative stress frequently observed in infection in vitro and in patients

·      To investigate how the above events drive fibrosis progression and hepatocarcinogenesis in infected patients

 

To find answers to these questions, we use a mixture of molecular and cellular biology, biochemistry, metabolomics, imaging and state of the art infection assays (P3 biosafety level). In addition, we have access to clinical cohorts and samples.

These studies will on the long term lead to the development of biomarkers and optimization of treatment modalities for fibrosis progression and prevention of hepatocarcinogenesis in viral hepatitis.

Selected publications from 2015-2017:

·      AV Ivanov, O Khomich, B Bartosch. Oxidative Stress in Hepatitis C infection; Bookchapter in  Liver Oxidative Stress and Dietary Antioxidants, edited by Vinood Patel. Elsevier. In press

·      O. Smirnova, T. Keinanen, O. Ivanova M. Hyvonen, A. Khomutov, S. Kochetkov, B. Bartosch, and A. Ivanov  Hepatitis C virus Alters metabolism of biogenic polyamines by affecting expression of key enzymes of their metabolism 2017 BBRC

·      AV Ivanov, VT Valuev-Elliston, DA Tyurina, ON Ivanova, SN Kochetkov, B Bartosch, MG Isaguliants Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis. 2017 Oncotarget

·      P.L. Lévy, S. Duponchel, H. Eischeid, M. Michelet, J. Molle, HP. Dienes, HM. Steffen, M. Odenthal, F. Zoulim, B. Bartosch. Hepatitis C virus infection triggers a tumor-like glutamine metabolism. 2017 Hepatology

·      A V. Ivanov, V T. Valuev-Elliston, O Ivanova, S N. Kochetkov, B Bartosch and M G. Isaguliants. Oxidative stress during HIV infection: mechanisms and consequences. 2016 Oxid Med Cell Longev

·      J  Rieusset ,  J  Fauconnier,  M  Paillard ,  E  Belaidi ,  E  Tubbs ,   M-A  Chauvin,  A  Durand ,  A  Bravard ,  G  Teixeira ,  B  Bartosch ,  M Michelet, P Theurey , G Vial , M Demion, E Blond , F Zoulim , L Gomez , H Vidal , A Lacampagne, M Ovize.  Disruption of calcium transfer from ER to mitochondria links alterations of mitochondria-associated endoplasmic reticulum membranes (MAM) integrity to hepatic insulin resistance. 2016 Diabetologia

·      Charlène Brault, Pierre Lévy, Sarah Duponchel, Maud Michelet, Aurèlie Sallé, Eve-Isabelle Pecheur, Marie-Laure Plissonnier, Romain Parent, Evelyne Véricel, Alexander V Ivanov, Münevver Demir, Hans-Michael Steffen, Margarete Odenthal, Fabien Zoulim, Birke Bartosch. Glutathione peroxidase 4 is reversibly induced by HCV to control lipid peroxidation and to increase virion infectivity. 2016 Gut

·      Pierre Lévy, Birke Bartosch, Metabolic reprogramming: a hallmark of viral oncogenesis. 2015 Oncogene

·      Bartosch B. Piecing together the key players of fibrosis in chronic hepatitis C: what roles do non-hepatic liver resident cell types play? 2015 Gut

 

 

R. PARENT GROUP

The netrin-1/UNC5 axis in chronic liver disease associated with liver cancer

Netrin-1 is a secreted molecule implicated in neural development. It has also been shown to be involved in the pathogenesis and treatment resistance of a substantial range of cancer types.

However, no study has been adressing the role of netrin-1 in the liver field for years. We have previously implemented several studies aiming at defining the role of the netrin-1  / UNC5A axis in chronic liver disease, using the HCV and the UPR models.

We have shown that:

-  Netrin-1 and HCV are reciprocal inducers in vitro and in patients, as seen from the increase in viral morphogenesis and viral entry, both phenomena converging toward an increase in the level of infectivity of HCV virions, in an EGFR-dependent manner. This functional association involving a cancer-related virus and netrin-1 argues for evaluating the implication of UNC5 receptor ligands in other oncogenic microbial species.

- The UNC5A dependence receptor counteracts HCV persistence through regulation of autophagy in a DAPK-dependent manner, and is dramatically decreased in all instances in HCC samples, and specifically by HCV in cirrhosis.

- Unlike several structurally related oncogenic transcripts (l-myc, c-myc, c-myb), netrin-1 messenger RNA was selected for translation during UPR both in human hepatocytes and in mice livers. Depletion of netrin-1 during UPR induces apoptosis, leading to cell death through an uncoordinated phenotype-5A/C-mediated involvement of protein phosphatase 2A and death-associated protein kinase 1 in vitro and in netrin transgenic mice. IRES-driven netrin-1 translation leads to the inhibition of UNC5A/DAPK1-mediated apoptosis in the hepatic context during UPR, a hallmark of chronic liver disease.

Our objectives are to define:

- The implication of netrin-1 in liver inflammation (current Labex funded PhD student)

- The implication of netrin-1 in HCC onset (current ANRS funded program involving also a research assistant)

Since netrin-1 upregulation spans a wide spectrum of liver diseases (Plos Biol 2016), such programs represent an important part of the Pathology program of the Zoulim Team, which lies besides the HBV basic and the HBV immunopathology program of the team.

 

Selected publications

 

1: Plissonnier ML, Lahlali T, Raab M, Michelet M, Romero-López C, Rivoire M, Strebhardt K, Durantel D, Levrero M, Mehlen P, Zoulim F, Parent R. Reciprocal antagonism between the netrin-1 receptor uncoordinated-phenotype-5A (UNC5A) and the hepatitis C virus. Oncogene. 2017 Aug 7. doi: 10.1038/onc.2017.271. [Epub ahead of print] PubMed PMID: 28783179.

 

2: Lahlali T, Plissonnier ML, Romero-López C, Michelet M, Ducarouge B, Berzal-Herranz A, Zoulim F, Mehlen P, Parent R. Netrin-1 Protects Hepatocytes Against Cell Death Through Sustained Translation During the Unfolded Protein Response. Cell Mol Gastroenterol Hepatol. 2016 Jan 9;2(3):281-301.e9. doi: 10.1016/j.jcmgh.2015.12.011. eCollection 2016 May. PubMed PMID: 28174720; PubMed  Central PMCID: PMC5042567.

 

3: Plissonnier ML, Lahlali T, Michelet M, Lebossé F, Cottarel J, Beer M, Neveu G, Durantel D, Bartosch B, Accardi R, Clément S, Paradisi A, Devouassoux-Shisheboran

M, Einav S, Mehlen P, Zoulim F, Parent R. Epidermal Growth Factor Receptor-Dependent Mutual Amplification between Netrin-1 and the Hepatitis C Virus. PLoS Biol. 2016 Mar 31;14(3):e1002421. doi: 10.1371/journal.pbio.1002421.  eCollection 2016 Mar. PubMed PMID: 27031829; PubMed Central PMCID: PMC4816328.

 

4: Plissonnier ML, Lahlali T, Mehlen P, Parent R. [Hepatitis C, EGFR, cirrhosis and netrin-1: potential implications for HCC onset]. Med Sci (Paris). 2016 Jun-Jul;32(6-7):566-8. doi: 10.1051/medsci/20163206013. Epub 2016 Jul 12. French. PubMed PMID: 27406760.

 

 

 

E-I PECHEUR GROUP

Heparans sulfates proteoglycans of the hepatic microenvironment in the infection and early carcinogenesis induced by the hepatotropic viruses B, C and delta.

Chronic viral hepatitis is responsible for 75 % of hepatocellular carcinomas (HCC), the 2nd most lethal cancer after lung cancer and the 5th in terms of world incidence. No adequate therapy is currently effective against HCC, the only option at that stage is liver transplantation.

The hepatitis C virus (HCV) chronically infects 180 million individuals, and although effective antiviral treatments are available, there remains difficult-to-treat patients, at great risk of developing HCC. Hepatitis B and delta affect 350 and 20 million people respectively. Due to the hepatitis B (HBV) and delta (HDV) viruses, they are major public health problems because of the diversity of viral genotypes, their fast dissemination, the severity of hepatic damages, the emergence of viral resistant variants, the insufficient pharmacological control with current therapies and the variable access to expensive treatments.

In this context, a better understanding of the infection cycles and of the early stages of viral oncogenesis will allow to propose new therapeutic strategies. In a first axis of research centered on HCV, we shall study the hepatocyte micro-environment during infection, and the changes it undergoes under the influence of oxidative stress generated by viral replication. These fundamental results will be used in a second axis to pave new therapeutic tracks, in particular against HBV and HDV.

> SHOW MORE

C. COMBET GROUP

Our group carries out researches about pathogen-induced cancers by means of Bioinformatics. We are particularly interested in hepatocellular carcinoma induced by hepatitis B and C viruses (HBV and HCV).

Our activities cover:
- Development of databases integrating sequence, structure and function of biological macromolecules
- Integration of protein sequence and structure Bioinformatics analysis tools as Web servers
- Next-generation sequencing (NGS) data analysis
- Structural Bioinformatics of proteins
- Applied bioinformatics

> SHOW MORE

PUBLICATIONS

Luangsay S, Gruffaz M, Isorce N, Testoni B, Michelet M, Faure-Dupuy S, Maadadi S, Ait-Goughoulte M, Parent R, Rivoire M, Javanbakht H, Lucifora J, Durantel D, Zoulim F. Early inhibition of hepatocyte innate responses by hepatitis B virus.  J Hepatol. 2015 Jul 26. pii: S0168-8278(15)00477-8. doi: 10.1016/j.jhep.2015.07.014. [Epub ahead of print]

Luangsay S, Ait-Goughoulte M, Michelet M, Floriot O, Bonnin M, Gruffaz M, Rivoire M, Fletcher S, Javanbakht H, Lucifora J, Zoulim F, Durantel D.
Expression and functionality of Toll- and RIG-like receptors in HepaRG cells. J Hepatol. 2015 Nov;63(5):1077-85. doi: 10.1016/j.jhep.2015.06.022. Epub 2015 Jul 3.

Reddy KR, Zeuzem S, Zoulim F, Weiland O, Horban A, Stanciu C, Villamil FG, Andreone P, George J, Dammers E, Fu M, Kurland D, Lenz O, Ouwerkerk-Mahadevan S, Verbinnen T, Scott J, Jessner W. Simeprevir versus telaprevir with peginterferon and ribavirin in previous null or partial responders with chronic hepatitis C virus genotype 1 infection (ATTAIN): a randomised, double-blind, non-inferiority phase 3 trial. Lancet Infect Dis. 2015 Jan;15(1):27-35. doi: 10.1016/S1473-3099(14)71002-3. Epub 2014 Dec 5. PubMed PMID: 25482330.
  
Zoulim F, Carosi G, Greenbloom S, Mazur W, Nguyen T, Jeffers L, Brunetto M, Yu S, Llamoso C. Quantification of HBsAg in nucleos(t)ide-naïve patients treated for chronic hepatitis B with entecavir with or without tenofovir in the BE-LOW study. J Hepatol. 2015 Jan;62(1):56-63. doi: 10.1016/j.jhep.2014.08.031. Epub 2014 Aug 28. PubMed PMID: 25176615.

Brault C, Lévy P, Duponchel S, Michelet M, Sallé A, Pécheur EI, Plissonnier ML, Parent R, Véricel E, Ivanov AV, Demir M, Steffen HM, Odenthal M, Zoulim F, Bartosch B. Glutathione peroxidase 4 is reversibly induced by HCV to control lipid peroxidation and to increase virion infectivity. Gut. 2014 Dec 16. pii: gutjnl-2014-307904. doi: 10.1136/gutjnl-2014-307904. [Epub ahead of print] PubMed
PMID: 25516417.
  
Charuworn P, Hengen PN, Aguilar Schall R, Dinh P, Ge D, Corsa A, Reesink HW, Zoulim F, Kitrinos KM. Baseline Interpatient Hepatitis B Viral Diversity Differentiates HBsAg Outcomes in Patients Treated With Tenofovir Disoproxil Fumarate. J Hepatol. 2014 Dec 13. pii: S0168-8278(14)00926-X. doi: 10.1016/j.jhep.2014.12.008. [Epub ahead of print] PubMed PMID: 25514556.
  
Arends P, Sonneveld MJ, Zoutendijk R, Carey I, Brown A, Fasano M, Mutimer D, Deterding K, Reijnders JG, Oo Y, Petersen J, van Bömmel F, de Knegt RJ, Santantonio T, Berg T, Welzel TM, Wedemeyer H, Buti M, Pradat P, Zoulim F, Hansen B, Janssen HL; for the VIRGIL Surveillance Study Group. Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B:limited role for risk scores in Caucasians. Gut. 2014 Jul 10. pii: gutjnl-2014-307023. doi: 10.1136/gutjnl-2014-307023. [Epub ahead of print] PubMed PMID: 25011935.

Lucifora J, Xia Y, Reisinger F, Zhang K, Stadler D, Cheng X, Sprinzl MF, Koppensteiner H, Makowska Z, Volz T, Remouchamps C, Chou WM, Thasler WE, Hüser N, Durantel D, Liang TJ, Münk C, Heim MH, Browning JL, Dejardin E, Dandri M, Schindler M, Heikenwalder M, Protzer U. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science. 2014 Mar 14;343(6176):1221-8. doi:  10.1126/science.1243462. Epub 2014 Feb 20. PubMed PMID: 24557838.

Lavocat F, Deny P, Pichoud C, Al Hawajri N, Kitrinos K, Borroto-Esoda K, Zoulim F. Similar evolution of hepatitis B virus quasispecies in patients with incomplete adefovir response receiving tenofovir/emtricitabine combination or tenofovir monotherapy. J Hepatol. 2013 Jun 3. Jordheim LP, Durantel D, Zoulim F, Dumontet C. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat Rev Drug Discov. 2013 Jun;12(6):447-64. 

Simonin Y, Vegna S, Akkari L, Gregoire D, Antoine E, Piette J, Floc'h N, Lassus P, Yu GY, Rosenberg AR, Karin M, Durantel D, Hibner U. Lymphotoxin signaling is initiated by the viral polymerase in HCV-linked tumorigenesis. PLoS Pathog. 2013 Mar;9(3):e1003234. 

Accardi R, Fathallah I, Gruffat H, Mariggi√≤ G, Le Calvez-Kelm F, Voegele C, Bartosch B, Hernandez-Vargas H, McKay J, Sylla BS, Manet E, Tommasino M. Epstein - Barr virus transforming protein LMP-1 alters B cells gene expression by promoting accumulation of the oncoprotein ΔNp73α. PLoS Pathog. 2013 Mar;9(3):e1003186. 

Lacombe K, Boyd A, Lavocat F, Pichoud C, Gozlan J, Miailhes P, Lascoux-Combe C, Vernet G, Girard PM, Zoulim F. High incidence of treatment-induced and vaccine-escape hepatitis B virus mutants among human immunodeficiency virus/hepatitis B-infected patients. Hepatology. 2013 Mar 6. 

Jammart B, Michelet M, Pecheur EI, Parent R, Bartosch B, Zoulim F, Durantel D. Very-low-density lipoprotein (VLDL)-producing and hepatitis C virus-replicating HepG2 cells secrete no more lipoviroparticles than VLDL-deficient Huh7.5 cells. J Virol. 2013 May;87(9):5065-80. 

Hayer J, Jadeau F, Deleage G, Kay A, Zoulim F, Combet C. HBVdb: a knowledge database for Hepatitis B Virus. Nucleic Acids Res. 2013 Jan;41(Database issue):D566-70. 

Gish R, Jia JD, Locarnini S, Zoulim F. Selection of chronic hepatitis B therapy with high barrier to resistance. Lancet Infect Dis. 2012 Apr;12(4):341-53. 

Billioud G, Pichoud C, Parent R, Zoulim F. Decreased infectivity of nucleoside analogs-resistant hepatitis B virus mutants. J Hepatol. 2012 Jun;56(6):1269-75. 

Zoulim F. Hepatitis: Treatment failure in chronic hepatitis B. Nat Rev Gastroenterol Hepatol. 2011 Jul 4;8(7):366-7.

CENTRE DE RECHERCHE EN CANCEROLOGIE DE LYON (CRCL)
UMR INSERM 1052 CNRS 5286 - CENTRE LEON BERARD
Copyright 2011. CRCL
SUIVEZ LES ACTUALITES
DU CRCL SUR TWITTER :