Novel HBsAg mutations correlate with hepatocellular carcinoma, hamper HBsAg secretion and promote cell proliferation in vitro
Identifieur interne : 000710 ( Main/Exploration ); précédent : 000709; suivant : 000711Novel HBsAg mutations correlate with hepatocellular carcinoma, hamper HBsAg secretion and promote cell proliferation in vitro
Auteurs : Romina Salpini [Italie] ; Matteo Surdo [Italie] ; Nadia Warner [Australie] ; Maria Francesca Cortese [Italie] ; Danny Colledge [Australie] ; Sally Soppe [Australie] ; Maria Concetta Bellocchi [Italie] ; Daniele Armenia [Italie] ; Luca Carioti [Italie] ; Fabio Continenza [Italie] ; Domenico Di Carlo [Italie] ; Patrizia Saccomandi [Italie] ; Carmen Mirabelli [Italie, France] ; Michela Pollicita [Italie] ; Roberta Longo [Italie] ; Sara Romano [Italie] ; Giuseppina Cappiello [Italie] ; Alberto Span [Italie] ; Pascale Trimoulet [France] ; Herve Fleury [France] ; Jacopo Vecchiet [Italie] ; Nerio Iapadre [Italie] ; Angelo Barlattani [Italie] ; Ada Bertoli [Italie] ; Terenzio Mari [Italie] ; Caterina Pasquazzi [Italie] ; Gabriele Missale [Italie] ; Cesare Sarrecchia [Italie] ; Elisa Orecchini [Italie] ; Alessandro Michienzi [Italie] ; Massimo Andreoni [Italie] ; Simona Francioso [Italie] ; Mario Angelico [Italie] ; Jens Verheyen [Allemagne] ; Francesca Ceccherini-Silberstein [Italie] ; Stephen Locarnini [Australie] ; Carlo Federico Perno [Italie] ; Valentina Svicher [Italie]Source :
- Oncotarget [ 1949-2553 ] ; 2017.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Analyse multivariée, Antigènes de surface du virus de l'hépatite B (génétique), Antigènes de surface du virus de l'hépatite B (métabolisme), Carcinome hépatocellulaire (anatomopathologie), Carcinome hépatocellulaire (virologie), Cycle cellulaire, Facteurs de risque, Femelle, Fréquence d'allèle, Génotype, Humains, Hépatite B chronique (anatomopathologie), Hépatite B chronique (virologie), Interactions hôte-pathogène, Mutation, Mâle, Prolifération cellulaire, Sujet âgé, Tumeurs du foie (anatomopathologie), Tumeurs du foie (virologie), Virus de l'hépatite B (génétique), Virus de l'hépatite B (métabolisme), Virus de l'hépatite B (physiologie).
- MESH :
- anatomopathologie : Carcinome hépatocellulaire, Hépatite B chronique, Tumeurs du foie.
- génétique : Antigènes de surface du virus de l'hépatite B, Virus de l'hépatite B.
- métabolisme : Antigènes de surface du virus de l'hépatite B, Virus de l'hépatite B.
- physiologie : Virus de l'hépatite B.
- virologie : Carcinome hépatocellulaire, Hépatite B chronique, Tumeurs du foie.
- Adulte, Adulte d'âge moyen, Analyse multivariée, Cycle cellulaire, Facteurs de risque, Femelle, Fréquence d'allèle, Génotype, Humains, Interactions hôte-pathogène, Mutation, Mâle, Prolifération cellulaire, Sujet âgé.
English descriptors
- KwdEn :
- Adult, Aged, Carcinoma, Hepatocellular (pathology), Carcinoma, Hepatocellular (virology), Cell Cycle, Cell Proliferation, Female, Gene Frequency, Genotype, Hepatitis B Surface Antigens (genetics), Hepatitis B Surface Antigens (metabolism), Hepatitis B virus (genetics), Hepatitis B virus (metabolism), Hepatitis B virus (physiology), Hepatitis B, Chronic (pathology), Hepatitis B, Chronic (virology), Host-Pathogen Interactions, Humans, Liver Neoplasms (pathology), Liver Neoplasms (virology), Male, Middle Aged, Multivariate Analysis, Mutation, Risk Factors.
- MESH :
- chemical , genetics : Hepatitis B Surface Antigens.
- chemical , metabolism : Hepatitis B Surface Antigens.
- genetics : Hepatitis B virus.
- metabolism : Hepatitis B virus.
- pathology : Carcinoma, Hepatocellular, Hepatitis B, Chronic, Liver Neoplasms.
- physiology : Hepatitis B virus.
- virology : Carcinoma, Hepatocellular, Hepatitis B, Chronic, Liver Neoplasms.
- Adult, Aged, Cell Cycle, Cell Proliferation, Female, Gene Frequency, Genotype, Host-Pathogen Interactions, Humans, Male, Middle Aged, Multivariate Analysis, Mutation, Risk Factors.
Abstract
An impaired HBsAg-secretion can increase HBV oncogenic-properties. Here, we investigate genetic-determinants in HBsAg correlated with HBV-induced hepatocellular carcinoma (HCC), and their impact on HBsAg-secretion and cell-proliferation.
This study included 128 chronically HBV-infected patients: 23 with HCC (73.9% D; 26.1% A HBV-genotype), and 105 without cirrhosis/HCC (72.4% D, 27.6% A) as reference-group. The impact of mutations on HBsAg-secretion was assessed by measuring the ratio [secreted/intracellular HBsAg] until day 5 post-transfection. The impact of mutations on cell-cycle advancement was assessed by flow-cytometry.
Two HBsAg mutations significantly correlated with HCC: P203Q (17.4% [4/23] in HCC vs 1.0% [1/105] in non-HCC, P=0.004); S210R (34.8% [8/23] in HCC vs 3.8% [4/105] in non-HCC, P <0.001); P203Q+S210R (17.4% [4/23] in HCC vs 0% [0/110] in non-HCC, P=0.001). Both mutations reside in trans-membrane C-terminal domain critical for HBsAg-secretion. In
Specific mutations in HBsAg C-terminus significantly correlate with HBV-induced HCC. They hamper HBsAg-secretion and are associated with increased cellular proliferation, supporting their involvement in HCC-development. The identification of viral genetic markers associated with HCC is critical to identify patients at higher HCC-risk that may deserve intensive liver monitoring, and/or early anti-HBV therapy.
Url:
DOI: 10.18632/oncotarget.14944
PubMed: 28152517
PubMed Central: 5362517
Affiliations:
- Allemagne, Australie, France, Italie
- Aquitaine, Latium, Nouvelle-Aquitaine, Île-de-France
- Bordeaux, Paris, Rome
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Le document en format XML
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Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Mirabelli, Carmen" sort="Mirabelli, Carmen" uniqKey="Mirabelli C" first="Carmen" last="Mirabelli">Carmen Mirabelli</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="A4"> Institut Pasteur, Unité de Biologie des Virus Entériques, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Institut Pasteur, Unité de Biologie des Virus Entériques, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Pollicita, Michela" sort="Pollicita, Michela" uniqKey="Pollicita M" first="Michela" last="Pollicita">Michela Pollicita</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Longo, Roberta" sort="Longo, Roberta" uniqKey="Longo R" first="Roberta" last="Longo">Roberta Longo</name><affiliation wicri:level="3"><nlm:aff id="A5"> Unit of Microbiology, “S. Pertini Hospital”, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Unit of Microbiology, “S. Pertini Hospital”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Romano, Sara" sort="Romano, Sara" uniqKey="Romano S" first="Sara" last="Romano">Sara Romano</name><affiliation wicri:level="3"><nlm:aff id="A5"> Unit of Microbiology, “S. Pertini Hospital”, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Unit of Microbiology, “S. Pertini Hospital”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Cappiello, Giuseppina" sort="Cappiello, Giuseppina" uniqKey="Cappiello G" first="Giuseppina" last="Cappiello">Giuseppina Cappiello</name><affiliation wicri:level="3"><nlm:aff id="A5"> Unit of Microbiology, “S. Pertini Hospital”, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Unit of Microbiology, “S. Pertini Hospital”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Span, Alberto" sort="Span, Alberto" uniqKey="Span A" first="Alberto" last="Span">Alberto Span</name><affiliation wicri:level="3"><nlm:aff id="A5"> Unit of Microbiology, “S. Pertini Hospital”, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Unit of Microbiology, “S. Pertini Hospital”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Trimoulet, Pascale" sort="Trimoulet, Pascale" uniqKey="Trimoulet P" first="Pascale" last="Trimoulet">Pascale Trimoulet</name><affiliation wicri:level="3"><nlm:aff id="A6"> Laboratoire de Microbiologie Fondamentale et Pathogénicité, Hôpital Pellegrin Tripode, Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Laboratoire de Microbiologie Fondamentale et Pathogénicité, Hôpital Pellegrin Tripode, Bordeaux</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Fleury, Herve" sort="Fleury, Herve" uniqKey="Fleury H" first="Herve" last="Fleury">Herve Fleury</name><affiliation wicri:level="3"><nlm:aff id="A6"> Laboratoire de Microbiologie Fondamentale et Pathogénicité, Hôpital Pellegrin Tripode, Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Laboratoire de Microbiologie Fondamentale et Pathogénicité, Hôpital Pellegrin Tripode, Bordeaux</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Vecchiet, Jacopo" sort="Vecchiet, Jacopo" uniqKey="Vecchiet J" first="Jacopo" last="Vecchiet">Jacopo Vecchiet</name><affiliation wicri:level="1"><nlm:aff id="A7"> Department of Medicine and Aging Sciences, “SS Annunziata” Hospital, Chieti, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Medicine and Aging Sciences, “SS Annunziata” Hospital, Chieti</wicri:regionArea><wicri:noRegion>Chieti</wicri:noRegion></affiliation></author><author><name sortKey="Iapadre, Nerio" sort="Iapadre, Nerio" uniqKey="Iapadre N" first="Nerio" last="Iapadre">Nerio Iapadre</name><affiliation wicri:level="1"><nlm:aff id="A8"> Infectious Diseases Unit, “S Salvatore” Hospital, L'Aquila, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Infectious Diseases Unit, “S Salvatore” Hospital, L'Aquila</wicri:regionArea><wicri:noRegion>L'Aquila</wicri:noRegion></affiliation></author><author><name sortKey="Barlattani, Angelo" sort="Barlattani, Angelo" uniqKey="Barlattani A" first="Angelo" last="Barlattani">Angelo Barlattani</name><affiliation wicri:level="3"><nlm:aff id="A9"> Hepatology Unit, “S Giacomo” Hospital, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Hepatology Unit, “S Giacomo” Hospital, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Bertoli, Ada" sort="Bertoli, Ada" uniqKey="Bertoli A" first="Ada" last="Bertoli">Ada Bertoli</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Mari, Terenzio" sort="Mari, Terenzio" uniqKey="Mari T" first="Terenzio" last="Mari">Terenzio Mari</name><affiliation wicri:level="3"><nlm:aff id="A10"> Hepatology Unit, “Regina Margherita” Hospital, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Hepatology Unit, “Regina Margherita” Hospital, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Pasquazzi, Caterina" sort="Pasquazzi, Caterina" uniqKey="Pasquazzi C" first="Caterina" last="Pasquazzi">Caterina Pasquazzi</name><affiliation wicri:level="3"><nlm:aff id="A11"> Hepato-Infectivology Unit, “S Andrea” Hospital, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Hepato-Infectivology Unit, “S Andrea” Hospital, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Missale, Gabriele" sort="Missale, Gabriele" uniqKey="Missale G" first="Gabriele" last="Missale">Gabriele Missale</name><affiliation wicri:level="1"><nlm:aff id="A12"> Hospital of Parma, Parma, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Hospital of Parma, Parma</wicri:regionArea><wicri:noRegion>Parma</wicri:noRegion></affiliation></author><author><name sortKey="Sarrecchia, Cesare" sort="Sarrecchia, Cesare" uniqKey="Sarrecchia C" first="Cesare" last="Sarrecchia">Cesare Sarrecchia</name><affiliation wicri:level="3"><nlm:aff id="A13"> Tor Vergata University Hospital, Infectious Diseases Unit, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Tor Vergata University Hospital, Infectious Diseases Unit, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Orecchini, Elisa" sort="Orecchini, Elisa" uniqKey="Orecchini E" first="Elisa" last="Orecchini">Elisa Orecchini</name><affiliation wicri:level="1"><nlm:aff id="A14"> Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Michienzi, Alessandro" sort="Michienzi, Alessandro" uniqKey="Michienzi A" first="Alessandro" last="Michienzi">Alessandro Michienzi</name><affiliation wicri:level="1"><nlm:aff id="A14"> Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Andreoni, Massimo" sort="Andreoni, Massimo" uniqKey="Andreoni M" first="Massimo" last="Andreoni">Massimo Andreoni</name><affiliation wicri:level="3"><nlm:aff id="A13"> Tor Vergata University Hospital, Infectious Diseases Unit, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Tor Vergata University Hospital, Infectious Diseases Unit, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Francioso, Simona" sort="Francioso, Simona" uniqKey="Francioso S" first="Simona" last="Francioso">Simona Francioso</name><affiliation wicri:level="3"><nlm:aff id="A15"> Tor Vergata University Hospital, Hepatology Unit, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Tor Vergata University Hospital, Hepatology Unit, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Angelico, Mario" sort="Angelico, Mario" uniqKey="Angelico M" first="Mario" last="Angelico">Mario Angelico</name><affiliation wicri:level="3"><nlm:aff id="A15"> Tor Vergata University Hospital, Hepatology Unit, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Tor Vergata University Hospital, Hepatology Unit, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Verheyen, Jens" sort="Verheyen, Jens" uniqKey="Verheyen J" first="Jens" last="Verheyen">Jens Verheyen</name><affiliation wicri:level="1"><nlm:aff id="A16"> Institute of Virology, University Hospital, University of Duisburg-Essen, Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea> Institute of Virology, University Hospital, University of Duisburg-Essen, Essen</wicri:regionArea><wicri:noRegion>Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion></affiliation></author><author><name sortKey="Ceccherini Silberstein, Francesca" sort="Ceccherini Silberstein, Francesca" uniqKey="Ceccherini Silberstein F" first="Francesca" last="Ceccherini-Silberstein">Francesca Ceccherini-Silberstein</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Locarnini, Stephen" sort="Locarnini, Stephen" uniqKey="Locarnini S" first="Stephen" last="Locarnini">Stephen Locarnini</name><affiliation wicri:level="1"><nlm:aff id="A2"> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Perno, Carlo Federico" sort="Perno, Carlo Federico" uniqKey="Perno C" first="Carlo Federico" last="Perno">Carlo Federico Perno</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Svicher, Valentina" sort="Svicher, Valentina" uniqKey="Svicher V" first="Valentina" last="Svicher">Valentina Svicher</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28152517</idno><idno type="pmc">5362517</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362517</idno><idno type="RBID">PMC:5362517</idno><idno type="doi">10.18632/oncotarget.14944</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">002836</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002836</idno><idno type="wicri:Area/Pmc/Curation">002686</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002686</idno><idno type="wicri:Area/Pmc/Checkpoint">000175</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000175</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">001081</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001081</idno><idno type="wicri:Area/PubMed/Curation">001078</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001078</idno><idno type="wicri:Area/PubMed/Checkpoint">001078</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001078</idno><idno type="wicri:Area/Ncbi/Merge">004259</idno><idno type="wicri:Area/Ncbi/Curation">004259</idno><idno type="wicri:Area/Ncbi/Checkpoint">004259</idno><idno type="wicri:Area/Main/Merge">000705</idno><idno type="wicri:Area/Main/Curation">000710</idno><idno type="wicri:Area/Main/Exploration">000710</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Novel HBsAg mutations correlate with hepatocellular carcinoma, hamper HBsAg secretion and promote cell proliferation <italic>in vitro</italic></title><author><name sortKey="Salpini, Romina" sort="Salpini, Romina" uniqKey="Salpini R" first="Romina" last="Salpini">Romina Salpini</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Surdo, Matteo" sort="Surdo, Matteo" uniqKey="Surdo M" first="Matteo" last="Surdo">Matteo Surdo</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Warner, Nadia" sort="Warner, Nadia" uniqKey="Warner N" first="Nadia" last="Warner">Nadia Warner</name><affiliation wicri:level="1"><nlm:aff id="A2"> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Cortese, Maria Francesca" sort="Cortese, Maria Francesca" uniqKey="Cortese M" first="Maria Francesca" last="Cortese">Maria Francesca Cortese</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Colledge, Danny" sort="Colledge, Danny" uniqKey="Colledge D" first="Danny" last="Colledge">Danny Colledge</name><affiliation wicri:level="1"><nlm:aff id="A2"> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Soppe, Sally" sort="Soppe, Sally" uniqKey="Soppe S" first="Sally" last="Soppe">Sally Soppe</name><affiliation wicri:level="1"><nlm:aff id="A2"> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Bellocchi, Maria Concetta" sort="Bellocchi, Maria Concetta" uniqKey="Bellocchi M" first="Maria Concetta" last="Bellocchi">Maria Concetta Bellocchi</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Armenia, Daniele" sort="Armenia, Daniele" uniqKey="Armenia D" first="Daniele" last="Armenia">Daniele Armenia</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Carioti, Luca" sort="Carioti, Luca" uniqKey="Carioti L" first="Luca" last="Carioti">Luca Carioti</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Continenza, Fabio" sort="Continenza, Fabio" uniqKey="Continenza F" first="Fabio" last="Continenza">Fabio Continenza</name><affiliation wicri:level="1"><nlm:aff id="A3"> Laboratory of Monitoring Antiviral Drugs, National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Laboratory of Monitoring Antiviral Drugs, National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani” Rome</wicri:regionArea><wicri:noRegion>National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Carlo, Domenico Di" sort="Carlo, Domenico Di" uniqKey="Carlo D" first="Domenico Di" last="Carlo">Domenico Di Carlo</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Saccomandi, Patrizia" sort="Saccomandi, Patrizia" uniqKey="Saccomandi P" first="Patrizia" last="Saccomandi">Patrizia Saccomandi</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Mirabelli, Carmen" sort="Mirabelli, Carmen" uniqKey="Mirabelli C" first="Carmen" last="Mirabelli">Carmen Mirabelli</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="A4"> Institut Pasteur, Unité de Biologie des Virus Entériques, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Institut Pasteur, Unité de Biologie des Virus Entériques, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Pollicita, Michela" sort="Pollicita, Michela" uniqKey="Pollicita M" first="Michela" last="Pollicita">Michela Pollicita</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Longo, Roberta" sort="Longo, Roberta" uniqKey="Longo R" first="Roberta" last="Longo">Roberta Longo</name><affiliation wicri:level="3"><nlm:aff id="A5"> Unit of Microbiology, “S. Pertini Hospital”, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Unit of Microbiology, “S. Pertini Hospital”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Romano, Sara" sort="Romano, Sara" uniqKey="Romano S" first="Sara" last="Romano">Sara Romano</name><affiliation wicri:level="3"><nlm:aff id="A5"> Unit of Microbiology, “S. Pertini Hospital”, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Unit of Microbiology, “S. Pertini Hospital”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Cappiello, Giuseppina" sort="Cappiello, Giuseppina" uniqKey="Cappiello G" first="Giuseppina" last="Cappiello">Giuseppina Cappiello</name><affiliation wicri:level="3"><nlm:aff id="A5"> Unit of Microbiology, “S. Pertini Hospital”, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Unit of Microbiology, “S. Pertini Hospital”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Span, Alberto" sort="Span, Alberto" uniqKey="Span A" first="Alberto" last="Span">Alberto Span</name><affiliation wicri:level="3"><nlm:aff id="A5"> Unit of Microbiology, “S. Pertini Hospital”, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Unit of Microbiology, “S. Pertini Hospital”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Trimoulet, Pascale" sort="Trimoulet, Pascale" uniqKey="Trimoulet P" first="Pascale" last="Trimoulet">Pascale Trimoulet</name><affiliation wicri:level="3"><nlm:aff id="A6"> Laboratoire de Microbiologie Fondamentale et Pathogénicité, Hôpital Pellegrin Tripode, Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Laboratoire de Microbiologie Fondamentale et Pathogénicité, Hôpital Pellegrin Tripode, Bordeaux</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Fleury, Herve" sort="Fleury, Herve" uniqKey="Fleury H" first="Herve" last="Fleury">Herve Fleury</name><affiliation wicri:level="3"><nlm:aff id="A6"> Laboratoire de Microbiologie Fondamentale et Pathogénicité, Hôpital Pellegrin Tripode, Bordeaux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Laboratoire de Microbiologie Fondamentale et Pathogénicité, Hôpital Pellegrin Tripode, Bordeaux</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Vecchiet, Jacopo" sort="Vecchiet, Jacopo" uniqKey="Vecchiet J" first="Jacopo" last="Vecchiet">Jacopo Vecchiet</name><affiliation wicri:level="1"><nlm:aff id="A7"> Department of Medicine and Aging Sciences, “SS Annunziata” Hospital, Chieti, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Medicine and Aging Sciences, “SS Annunziata” Hospital, Chieti</wicri:regionArea><wicri:noRegion>Chieti</wicri:noRegion></affiliation></author><author><name sortKey="Iapadre, Nerio" sort="Iapadre, Nerio" uniqKey="Iapadre N" first="Nerio" last="Iapadre">Nerio Iapadre</name><affiliation wicri:level="1"><nlm:aff id="A8"> Infectious Diseases Unit, “S Salvatore” Hospital, L'Aquila, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Infectious Diseases Unit, “S Salvatore” Hospital, L'Aquila</wicri:regionArea><wicri:noRegion>L'Aquila</wicri:noRegion></affiliation></author><author><name sortKey="Barlattani, Angelo" sort="Barlattani, Angelo" uniqKey="Barlattani A" first="Angelo" last="Barlattani">Angelo Barlattani</name><affiliation wicri:level="3"><nlm:aff id="A9"> Hepatology Unit, “S Giacomo” Hospital, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Hepatology Unit, “S Giacomo” Hospital, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Bertoli, Ada" sort="Bertoli, Ada" uniqKey="Bertoli A" first="Ada" last="Bertoli">Ada Bertoli</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Mari, Terenzio" sort="Mari, Terenzio" uniqKey="Mari T" first="Terenzio" last="Mari">Terenzio Mari</name><affiliation wicri:level="3"><nlm:aff id="A10"> Hepatology Unit, “Regina Margherita” Hospital, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Hepatology Unit, “Regina Margherita” Hospital, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Pasquazzi, Caterina" sort="Pasquazzi, Caterina" uniqKey="Pasquazzi C" first="Caterina" last="Pasquazzi">Caterina Pasquazzi</name><affiliation wicri:level="3"><nlm:aff id="A11"> Hepato-Infectivology Unit, “S Andrea” Hospital, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Hepato-Infectivology Unit, “S Andrea” Hospital, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Missale, Gabriele" sort="Missale, Gabriele" uniqKey="Missale G" first="Gabriele" last="Missale">Gabriele Missale</name><affiliation wicri:level="1"><nlm:aff id="A12"> Hospital of Parma, Parma, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Hospital of Parma, Parma</wicri:regionArea><wicri:noRegion>Parma</wicri:noRegion></affiliation></author><author><name sortKey="Sarrecchia, Cesare" sort="Sarrecchia, Cesare" uniqKey="Sarrecchia C" first="Cesare" last="Sarrecchia">Cesare Sarrecchia</name><affiliation wicri:level="3"><nlm:aff id="A13"> Tor Vergata University Hospital, Infectious Diseases Unit, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Tor Vergata University Hospital, Infectious Diseases Unit, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Orecchini, Elisa" sort="Orecchini, Elisa" uniqKey="Orecchini E" first="Elisa" last="Orecchini">Elisa Orecchini</name><affiliation wicri:level="1"><nlm:aff id="A14"> Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Michienzi, Alessandro" sort="Michienzi, Alessandro" uniqKey="Michienzi A" first="Alessandro" last="Michienzi">Alessandro Michienzi</name><affiliation wicri:level="1"><nlm:aff id="A14"> Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Biomedicine and Prevention, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Andreoni, Massimo" sort="Andreoni, Massimo" uniqKey="Andreoni M" first="Massimo" last="Andreoni">Massimo Andreoni</name><affiliation wicri:level="3"><nlm:aff id="A13"> Tor Vergata University Hospital, Infectious Diseases Unit, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Tor Vergata University Hospital, Infectious Diseases Unit, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Francioso, Simona" sort="Francioso, Simona" uniqKey="Francioso S" first="Simona" last="Francioso">Simona Francioso</name><affiliation wicri:level="3"><nlm:aff id="A15"> Tor Vergata University Hospital, Hepatology Unit, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Tor Vergata University Hospital, Hepatology Unit, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Angelico, Mario" sort="Angelico, Mario" uniqKey="Angelico M" first="Mario" last="Angelico">Mario Angelico</name><affiliation wicri:level="3"><nlm:aff id="A15"> Tor Vergata University Hospital, Hepatology Unit, Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Tor Vergata University Hospital, Hepatology Unit, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Verheyen, Jens" sort="Verheyen, Jens" uniqKey="Verheyen J" first="Jens" last="Verheyen">Jens Verheyen</name><affiliation wicri:level="1"><nlm:aff id="A16"> Institute of Virology, University Hospital, University of Duisburg-Essen, Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea> Institute of Virology, University Hospital, University of Duisburg-Essen, Essen</wicri:regionArea><wicri:noRegion>Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion></affiliation></author><author><name sortKey="Ceccherini Silberstein, Francesca" sort="Ceccherini Silberstein, Francesca" uniqKey="Ceccherini Silberstein F" first="Francesca" last="Ceccherini-Silberstein">Francesca Ceccherini-Silberstein</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Locarnini, Stephen" sort="Locarnini, Stephen" uniqKey="Locarnini S" first="Stephen" last="Locarnini">Stephen Locarnini</name><affiliation wicri:level="1"><nlm:aff id="A2"> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Perno, Carlo Federico" sort="Perno, Carlo Federico" uniqKey="Perno C" first="Carlo Federico" last="Perno">Carlo Federico Perno</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author><author><name sortKey="Svicher, Valentina" sort="Svicher, Valentina" uniqKey="Svicher V" first="Valentina" last="Svicher">Valentina Svicher</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata” Rome</wicri:regionArea><wicri:noRegion>University of Rome “Tor Vergata” Rome</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncotarget</title><idno type="eISSN">1949-2553</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Carcinoma, Hepatocellular (pathology)</term><term>Carcinoma, Hepatocellular (virology)</term><term>Cell Cycle</term><term>Cell Proliferation</term><term>Female</term><term>Gene Frequency</term><term>Genotype</term><term>Hepatitis B Surface Antigens (genetics)</term><term>Hepatitis B Surface Antigens (metabolism)</term><term>Hepatitis B virus (genetics)</term><term>Hepatitis B virus (metabolism)</term><term>Hepatitis B virus (physiology)</term><term>Hepatitis B, Chronic (pathology)</term><term>Hepatitis B, Chronic (virology)</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Liver Neoplasms (pathology)</term><term>Liver Neoplasms (virology)</term><term>Male</term><term>Middle Aged</term><term>Multivariate Analysis</term><term>Mutation</term><term>Risk Factors</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse multivariée</term><term>Antigènes de surface du virus de l'hépatite B (génétique)</term><term>Antigènes de surface du virus de l'hépatite B (métabolisme)</term><term>Carcinome hépatocellulaire (anatomopathologie)</term><term>Carcinome hépatocellulaire (virologie)</term><term>Cycle cellulaire</term><term>Facteurs de risque</term><term>Femelle</term><term>Fréquence d'allèle</term><term>Génotype</term><term>Humains</term><term>Hépatite B chronique (anatomopathologie)</term><term>Hépatite B chronique (virologie)</term><term>Interactions hôte-pathogène</term><term>Mutation</term><term>Mâle</term><term>Prolifération cellulaire</term><term>Sujet âgé</term><term>Tumeurs du foie (anatomopathologie)</term><term>Tumeurs du foie (virologie)</term><term>Virus de l'hépatite B (génétique)</term><term>Virus de l'hépatite B (métabolisme)</term><term>Virus de l'hépatite B (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hepatitis B Surface Antigens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Hepatitis B Surface Antigens</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome hépatocellulaire</term><term>Hépatite B chronique</term><term>Tumeurs du foie</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Hepatitis B virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes de surface du virus de l'hépatite B</term><term>Virus de l'hépatite B</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Hepatitis B virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes de surface du virus de l'hépatite B</term><term>Virus de l'hépatite B</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Carcinoma, Hepatocellular</term><term>Hepatitis B, Chronic</term><term>Liver Neoplasms</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus de l'hépatite B</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Hepatitis B virus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Carcinome hépatocellulaire</term><term>Hépatite B chronique</term><term>Tumeurs du foie</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Carcinoma, Hepatocellular</term><term>Hepatitis B, Chronic</term><term>Liver Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Cell Cycle</term><term>Cell Proliferation</term><term>Female</term><term>Gene Frequency</term><term>Genotype</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Multivariate Analysis</term><term>Mutation</term><term>Risk Factors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse multivariée</term><term>Cycle cellulaire</term><term>Facteurs de risque</term><term>Femelle</term><term>Fréquence d'allèle</term><term>Génotype</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Mutation</term><term>Mâle</term><term>Prolifération cellulaire</term><term>Sujet âgé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>An impaired HBsAg-secretion can increase HBV oncogenic-properties. Here, we investigate genetic-determinants in HBsAg correlated with HBV-induced hepatocellular carcinoma (HCC), and their impact on HBsAg-secretion and cell-proliferation.</p></sec><sec><title>Methods</title><p>This study included 128 chronically HBV-infected patients: 23 with HCC (73.9% D; 26.1% A HBV-genotype), and 105 without cirrhosis/HCC (72.4% D, 27.6% A) as reference-group. The impact of mutations on HBsAg-secretion was assessed by measuring the ratio [secreted/intracellular HBsAg] until day 5 post-transfection. The impact of mutations on cell-cycle advancement was assessed by flow-cytometry.</p></sec><sec><title>Results</title><p>Two HBsAg mutations significantly correlated with HCC: P203Q (17.4% [4/23] in HCC vs 1.0% [1/105] in non-HCC, P=0.004); S210R (34.8% [8/23] in HCC vs 3.8% [4/105] in non-HCC, P <0.001); P203Q+S210R (17.4% [4/23] in HCC vs 0% [0/110] in non-HCC, P=0.001). Both mutations reside in trans-membrane C-terminal domain critical for HBsAg-secretion. In <italic>in-vitro</italic> experiments, P203Q, S210R and P203Q+S210R significantly reduced the ratio [secreted/intracellular HBsAg] compared to wt at each time-point analysed (P <0.05), supporting an impaired HBsAg-secretion. Furthermore, P203Q and P203Q+S210R increased the percentage of cells in S-phase compared to wt, indicating cell-cycle progression (P203Q:26±13%; P203Q+S210R:29±14%; wt:18%±9, P <0.01. Additionally, S210R increased the percentage of cells in G2/M-phase (26±8% for wt versus 33±6% for S210R, P <0.001).</p></sec><sec><title>Conclusions</title><p>Specific mutations in HBsAg C-terminus significantly correlate with HBV-induced HCC. They hamper HBsAg-secretion and are associated with increased cellular proliferation, supporting their involvement in HCC-development. 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uniqKey="Kim B">BJ Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Hc" uniqKey="Wang H">HC Wang</name></author><author><name sortKey="Chang, Wt" uniqKey="Chang W">WT Chang</name></author><author><name sortKey="Chang, Ww" uniqKey="Chang W">WW Chang</name></author><author><name sortKey="Wu, Hc" uniqKey="Wu H">HC Wu</name></author><author><name sortKey="Huang, W" uniqKey="Huang W">W Huang</name></author><author><name sortKey="Lei, Hy" uniqKey="Lei H">HY Lei</name></author><author><name sortKey="Lai, Md" uniqKey="Lai M">MD Lai</name></author><author><name sortKey="Fausto, N" uniqKey="Fausto N">N Fausto</name></author><author><name sortKey="Su, Ij" uniqKey="Su I">IJ Su</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aaltomaa, S" uniqKey="Aaltomaa S">S Aaltomaa</name></author><author><name sortKey="Eskelinen, M" uniqKey="Eskelinen M">M Eskelinen</name></author><author><name sortKey="Lipponen, P" uniqKey="Lipponen P">P Lipponen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aaltomaa, S" uniqKey="Aaltomaa S">S Aaltomaa</name></author><author><name sortKey="Lipponen, P" uniqKey="Lipponen P">P Lipponen</name></author><author><name sortKey="Ala Opas, M" uniqKey="Ala Opas M">M Ala-Opas</name></author><author><name sortKey="Eskelinen, M" uniqKey="Eskelinen M">M Eskelinen</name></author><author><name sortKey="Syrjanen, K" uniqKey="Syrjanen K">K Syrjanen</name></author><author><name sortKey="Kosma, Vm" uniqKey="Kosma V">VM Kosma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Jq" uniqKey="Li J">JQ Li</name></author><author><name sortKey="Miki, H" uniqKey="Miki H">H Miki</name></author><author><name sortKey="Wu, F" uniqKey="Wu F">F Wu</name></author><author><name sortKey="Saoo, K" uniqKey="Saoo K">K Saoo</name></author><author><name sortKey="Nishioka, M" uniqKey="Nishioka M">M Nishioka</name></author><author><name sortKey="Ohmori, M" uniqKey="Ohmori M">M Ohmori</name></author><author><name sortKey="Imaida, K" uniqKey="Imaida K">K Imaida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author><author><name sortKey="Sun, Jw" uniqKey="Sun J">JW Sun</name></author><author><name sortKey="Zhao, Lg" uniqKey="Zhao L">LG Zhao</name></author><author><name sortKey="Bray, F" uniqKey="Bray F">F Bray</name></author><author><name sortKey="Xiang, Yb" uniqKey="Xiang Y">YB Xiang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Italie</li></country><region><li>Aquitaine</li><li>Latium</li><li>Nouvelle-Aquitaine</li><li>Île-de-France</li></region><settlement><li>Bordeaux</li><li>Paris</li><li>Rome</li></settlement></list><tree><country name="Italie"><noRegion><name sortKey="Salpini, Romina" sort="Salpini, Romina" uniqKey="Salpini R" first="Romina" last="Salpini">Romina Salpini</name></noRegion><name sortKey="Andreoni, Massimo" sort="Andreoni, Massimo" uniqKey="Andreoni M" first="Massimo" last="Andreoni">Massimo Andreoni</name><name sortKey="Angelico, Mario" sort="Angelico, Mario" uniqKey="Angelico M" first="Mario" last="Angelico">Mario Angelico</name><name sortKey="Armenia, Daniele" sort="Armenia, Daniele" uniqKey="Armenia D" first="Daniele" last="Armenia">Daniele Armenia</name><name sortKey="Barlattani, Angelo" sort="Barlattani, Angelo" uniqKey="Barlattani A" first="Angelo" last="Barlattani">Angelo Barlattani</name><name sortKey="Bellocchi, Maria Concetta" sort="Bellocchi, Maria Concetta" uniqKey="Bellocchi M" first="Maria Concetta" last="Bellocchi">Maria Concetta Bellocchi</name><name sortKey="Bertoli, Ada" sort="Bertoli, Ada" uniqKey="Bertoli A" first="Ada" last="Bertoli">Ada Bertoli</name><name sortKey="Cappiello, Giuseppina" sort="Cappiello, Giuseppina" uniqKey="Cappiello G" first="Giuseppina" last="Cappiello">Giuseppina Cappiello</name><name sortKey="Carioti, Luca" sort="Carioti, Luca" uniqKey="Carioti L" first="Luca" last="Carioti">Luca Carioti</name><name sortKey="Carlo, Domenico Di" sort="Carlo, Domenico Di" uniqKey="Carlo D" first="Domenico Di" last="Carlo">Domenico Di Carlo</name><name sortKey="Ceccherini Silberstein, Francesca" sort="Ceccherini Silberstein, Francesca" uniqKey="Ceccherini Silberstein F" first="Francesca" last="Ceccherini-Silberstein">Francesca Ceccherini-Silberstein</name><name sortKey="Continenza, Fabio" sort="Continenza, Fabio" uniqKey="Continenza F" first="Fabio" last="Continenza">Fabio Continenza</name><name sortKey="Cortese, Maria Francesca" sort="Cortese, Maria Francesca" uniqKey="Cortese M" first="Maria Francesca" last="Cortese">Maria Francesca Cortese</name><name sortKey="Francioso, Simona" sort="Francioso, Simona" uniqKey="Francioso S" first="Simona" last="Francioso">Simona Francioso</name><name sortKey="Iapadre, Nerio" sort="Iapadre, Nerio" uniqKey="Iapadre N" first="Nerio" last="Iapadre">Nerio Iapadre</name><name sortKey="Longo, Roberta" sort="Longo, Roberta" uniqKey="Longo R" first="Roberta" last="Longo">Roberta Longo</name><name sortKey="Mari, Terenzio" sort="Mari, Terenzio" uniqKey="Mari T" first="Terenzio" last="Mari">Terenzio Mari</name><name sortKey="Michienzi, Alessandro" sort="Michienzi, Alessandro" uniqKey="Michienzi A" first="Alessandro" last="Michienzi">Alessandro Michienzi</name><name sortKey="Mirabelli, Carmen" sort="Mirabelli, Carmen" uniqKey="Mirabelli C" first="Carmen" last="Mirabelli">Carmen Mirabelli</name><name sortKey="Missale, Gabriele" sort="Missale, Gabriele" uniqKey="Missale G" first="Gabriele" last="Missale">Gabriele Missale</name><name sortKey="Orecchini, Elisa" sort="Orecchini, Elisa" uniqKey="Orecchini E" first="Elisa" last="Orecchini">Elisa Orecchini</name><name sortKey="Pasquazzi, Caterina" sort="Pasquazzi, Caterina" uniqKey="Pasquazzi C" first="Caterina" last="Pasquazzi">Caterina Pasquazzi</name><name sortKey="Perno, Carlo Federico" sort="Perno, Carlo Federico" uniqKey="Perno C" first="Carlo Federico" last="Perno">Carlo Federico Perno</name><name sortKey="Pollicita, Michela" sort="Pollicita, Michela" uniqKey="Pollicita M" first="Michela" last="Pollicita">Michela Pollicita</name><name sortKey="Romano, Sara" sort="Romano, Sara" uniqKey="Romano S" first="Sara" last="Romano">Sara Romano</name><name sortKey="Saccomandi, Patrizia" sort="Saccomandi, Patrizia" uniqKey="Saccomandi P" first="Patrizia" last="Saccomandi">Patrizia Saccomandi</name><name sortKey="Sarrecchia, Cesare" sort="Sarrecchia, Cesare" uniqKey="Sarrecchia C" first="Cesare" last="Sarrecchia">Cesare Sarrecchia</name><name sortKey="Span, Alberto" sort="Span, Alberto" uniqKey="Span A" first="Alberto" last="Span">Alberto Span</name><name sortKey="Surdo, Matteo" sort="Surdo, Matteo" uniqKey="Surdo M" first="Matteo" last="Surdo">Matteo Surdo</name><name sortKey="Svicher, Valentina" sort="Svicher, Valentina" uniqKey="Svicher V" first="Valentina" last="Svicher">Valentina Svicher</name><name sortKey="Vecchiet, Jacopo" sort="Vecchiet, Jacopo" uniqKey="Vecchiet J" first="Jacopo" last="Vecchiet">Jacopo Vecchiet</name></country><country name="Australie"><noRegion><name sortKey="Warner, Nadia" sort="Warner, Nadia" uniqKey="Warner N" first="Nadia" last="Warner">Nadia Warner</name></noRegion><name sortKey="Colledge, Danny" sort="Colledge, Danny" uniqKey="Colledge D" first="Danny" last="Colledge">Danny Colledge</name><name sortKey="Locarnini, Stephen" sort="Locarnini, Stephen" uniqKey="Locarnini S" first="Stephen" last="Locarnini">Stephen Locarnini</name><name sortKey="Soppe, Sally" sort="Soppe, Sally" uniqKey="Soppe S" first="Sally" last="Soppe">Sally Soppe</name></country><country name="France"><region name="Île-de-France"><name sortKey="Mirabelli, Carmen" sort="Mirabelli, Carmen" uniqKey="Mirabelli C" first="Carmen" last="Mirabelli">Carmen Mirabelli</name></region><name sortKey="Fleury, Herve" sort="Fleury, Herve" uniqKey="Fleury H" first="Herve" last="Fleury">Herve Fleury</name><name sortKey="Trimoulet, Pascale" sort="Trimoulet, Pascale" uniqKey="Trimoulet P" first="Pascale" last="Trimoulet">Pascale Trimoulet</name></country><country name="Allemagne"><noRegion><name sortKey="Verheyen, Jens" sort="Verheyen, Jens" uniqKey="Verheyen J" first="Jens" last="Verheyen">Jens Verheyen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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