Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.
Identifieur interne : 002237 ( Main/Exploration ); précédent : 002236; suivant : 002238Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.
Auteurs : A. Velay [France] ; H. Jeulin [France] ; M. Eschlimann [France] ; B. Malvé [France] ; F. Goehringer [France] ; M. Bensenane [France] ; J-P Frippiat [France] ; P. Abraham [Inde] ; A M Ismail [Inde] ; J M Murray [Australie] ; C. Combet [France] ; F. Zoulim [France] ; J-P Bronowicki [France] ; E. Schvoerer [France]Source :
- Journal of viral hepatitis [ 1365-2893 ] ; 2016.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Analyse de séquence d'ADN, Animaux, Antigènes de surface du virus de l'hépatite B (génétique), Antigènes de surface du virus de l'hépatite B (immunologie), Antiviraux (usage thérapeutique), Biologie informatique, Femelle, Humains, Hépatite B chronique (traitement médicamenteux), Mâle, Nucléosides (usage thérapeutique), Nucléotides (usage thérapeutique), Protéines mutantes (génétique), Protéines mutantes (immunologie), Souris de lignée BALB C, Substitution d'acide aminé, Sujet âgé, Test ELISA, Variation des antigènes, Variation génétique.
- MESH :
- génétique : Antigènes de surface du virus de l'hépatite B, Protéines mutantes.
- immunologie : Antigènes de surface du virus de l'hépatite B, Protéines mutantes.
- traitement médicamenteux : Hépatite B chronique.
- usage thérapeutique : Antiviraux, Nucléosides, Nucléotides.
- Adulte, Adulte d'âge moyen, Analyse de séquence d'ADN, Animaux, Biologie informatique, Femelle, Humains, Mâle, Souris de lignée BALB C, Substitution d'acide aminé, Sujet âgé, Test ELISA, Variation des antigènes, Variation génétique.
English descriptors
- KwdEn :
- Adult, Aged, Amino Acid Substitution, Animals, Antigenic Variation, Antiviral Agents (therapeutic use), Computational Biology, Enzyme-Linked Immunosorbent Assay, Female, Genetic Variation, Hepatitis B Surface Antigens (genetics), Hepatitis B Surface Antigens (immunology), Hepatitis B, Chronic (drug therapy), Humans, Male, Mice, Inbred BALB C, Middle Aged, Mutant Proteins (genetics), Mutant Proteins (immunology), Nucleosides (therapeutic use), Nucleotides (therapeutic use), Sequence Analysis, DNA.
- MESH :
- chemical , genetics : Hepatitis B Surface Antigens, Mutant Proteins.
- chemical , immunology : Hepatitis B Surface Antigens, Mutant Proteins.
- chemical , therapeutic use : Antiviral Agents, Nucleosides, Nucleotides.
- drug therapy : Hepatitis B, Chronic.
- Adult, Aged, Amino Acid Substitution, Animals, Antigenic Variation, Computational Biology, Enzyme-Linked Immunosorbent Assay, Female, Genetic Variation, Humans, Male, Mice, Inbred BALB C, Middle Aged, Sequence Analysis, DNA.
Abstract
For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence.
DOI: 10.1111/jvh.12498
PubMed: 26742490
Affiliations:
- Australie, France, Inde
- Auvergne-Rhône-Alpes, Grand Est, Lorraine (région), Rhône-Alpes
- Lyon, Nancy, Vandœuvre-lès-Nancy
- Université de Lorraine
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Le document en format XML
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Malvé</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Goehringer, F" sort="Goehringer, F" uniqKey="Goehringer F" first="F" last="Goehringer">F. Goehringer</name><affiliation wicri:level="3"><nlm:affiliation>Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Bensenane, M" sort="Bensenane, M" uniqKey="Bensenane M" first="M" last="Bensenane">M. Bensenane</name><affiliation wicri:level="3"><nlm:affiliation>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Frippiat, J P" sort="Frippiat, J P" uniqKey="Frippiat J" first="J-P" last="Frippiat">J-P Frippiat</name><affiliation wicri:level="4"><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement><settlement type="city">Nancy</settlement></placeName><orgName type="university">Université de Lorraine</orgName></affiliation></author><author><name sortKey="Abraham, P" sort="Abraham, P" uniqKey="Abraham P" first="P" last="Abraham">P. Abraham</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu</wicri:regionArea><wicri:noRegion>Tamil Nadu</wicri:noRegion></affiliation></author><author><name sortKey="Ismail, A M" sort="Ismail, A M" uniqKey="Ismail A" first="A M" last="Ismail">A M Ismail</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu</wicri:regionArea><wicri:noRegion>Tamil Nadu</wicri:noRegion></affiliation></author><author><name sortKey="Murray, J M" sort="Murray, J M" uniqKey="Murray J" first="J M" last="Murray">J M Murray</name><affiliation wicri:level="1"><nlm:affiliation>School of Mathematics and Statistics, UNSW Australia, Sydney, NSW, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Mathematics and Statistics, UNSW Australia, Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Combet, C" sort="Combet, C" uniqKey="Combet C" first="C" last="Combet">C. Combet</name><affiliation wicri:level="3"><nlm:affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité Inserm UI1052, Université de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Zoulim, F" sort="Zoulim, F" uniqKey="Zoulim F" first="F" last="Zoulim">F. Zoulim</name><affiliation wicri:level="3"><nlm:affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité Inserm UI1052, Université de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Bronowicki, J P" sort="Bronowicki, J P" uniqKey="Bronowicki J" first="J-P" last="Bronowicki">J-P Bronowicki</name><affiliation wicri:level="3"><nlm:affiliation>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Schvoerer, E" sort="Schvoerer, E" uniqKey="Schvoerer E" first="E" last="Schvoerer">E. Schvoerer</name><affiliation wicri:level="4"><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement><settlement type="city">Nancy</settlement></placeName><orgName type="university">Université de Lorraine</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26742490</idno><idno type="pmid">26742490</idno><idno type="doi">10.1111/jvh.12498</idno><idno type="wicri:Area/PubMed/Corpus">001E94</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001E94</idno><idno type="wicri:Area/PubMed/Curation">001E70</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001E70</idno><idno type="wicri:Area/PubMed/Checkpoint">001E70</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001E70</idno><idno type="wicri:Area/Ncbi/Merge">002F56</idno><idno type="wicri:Area/Ncbi/Curation">002F56</idno><idno type="wicri:Area/Ncbi/Checkpoint">002F56</idno><idno type="wicri:Area/Main/Merge">002236</idno><idno type="wicri:Area/Main/Curation">002237</idno><idno type="wicri:Area/Main/Exploration">002237</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy.</title><author><name sortKey="Velay, A" sort="Velay, A" uniqKey="Velay A" first="A" last="Velay">A. Velay</name><affiliation wicri:level="4"><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement><settlement type="city">Nancy</settlement></placeName><orgName type="university">Université de Lorraine</orgName></affiliation></author><author><name sortKey="Jeulin, H" sort="Jeulin, H" uniqKey="Jeulin H" first="H" last="Jeulin">H. Jeulin</name><affiliation wicri:level="4"><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement><settlement type="city">Nancy</settlement></placeName><orgName type="university">Université de Lorraine</orgName></affiliation></author><author><name sortKey="Eschlimann, M" sort="Eschlimann, M" uniqKey="Eschlimann M" first="M" last="Eschlimann">M. Eschlimann</name><affiliation wicri:level="4"><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement><settlement type="city">Nancy</settlement></placeName><orgName type="university">Université de Lorraine</orgName></affiliation></author><author><name sortKey="Malve, B" sort="Malve, B" uniqKey="Malve B" first="B" last="Malvé">B. Malvé</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Goehringer, F" sort="Goehringer, F" uniqKey="Goehringer F" first="F" last="Goehringer">F. Goehringer</name><affiliation wicri:level="3"><nlm:affiliation>Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Bensenane, M" sort="Bensenane, M" uniqKey="Bensenane M" first="M" last="Bensenane">M. Bensenane</name><affiliation wicri:level="3"><nlm:affiliation>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Frippiat, J P" sort="Frippiat, J P" uniqKey="Frippiat J" first="J-P" last="Frippiat">J-P Frippiat</name><affiliation wicri:level="4"><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement><settlement type="city">Nancy</settlement></placeName><orgName type="university">Université de Lorraine</orgName></affiliation></author><author><name sortKey="Abraham, P" sort="Abraham, P" uniqKey="Abraham P" first="P" last="Abraham">P. Abraham</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu</wicri:regionArea><wicri:noRegion>Tamil Nadu</wicri:noRegion></affiliation></author><author><name sortKey="Ismail, A M" sort="Ismail, A M" uniqKey="Ismail A" first="A M" last="Ismail">A M Ismail</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu</wicri:regionArea><wicri:noRegion>Tamil Nadu</wicri:noRegion></affiliation></author><author><name sortKey="Murray, J M" sort="Murray, J M" uniqKey="Murray J" first="J M" last="Murray">J M Murray</name><affiliation wicri:level="1"><nlm:affiliation>School of Mathematics and Statistics, UNSW Australia, Sydney, NSW, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Mathematics and Statistics, UNSW Australia, Sydney, NSW</wicri:regionArea><wicri:noRegion>NSW</wicri:noRegion></affiliation></author><author><name sortKey="Combet, C" sort="Combet, C" uniqKey="Combet C" first="C" last="Combet">C. Combet</name><affiliation wicri:level="3"><nlm:affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité Inserm UI1052, Université de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Zoulim, F" sort="Zoulim, F" uniqKey="Zoulim F" first="F" last="Zoulim">F. Zoulim</name><affiliation wicri:level="3"><nlm:affiliation>Unité Inserm UI1052, Université de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité Inserm UI1052, Université de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Bronowicki, J P" sort="Bronowicki, J P" uniqKey="Bronowicki J" first="J-P" last="Bronowicki">J-P Bronowicki</name><affiliation wicri:level="3"><nlm:affiliation>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Schvoerer, E" sort="Schvoerer, E" uniqKey="Schvoerer E" first="E" last="Schvoerer">E. Schvoerer</name><affiliation wicri:level="4"><nlm:affiliation>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA 7300 'Stress, Immunité, Pathogènes', Université de Lorraine, Vandoeuvre-les-Nancy</wicri:regionArea><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandœuvre-lès-Nancy</settlement><settlement type="city" wicri:auto="agglo">Nancy</settlement><settlement type="city">Nancy</settlement></placeName><orgName type="university">Université de Lorraine</orgName></affiliation></author></analytic><series><title level="j">Journal of viral hepatitis</title><idno type="eISSN">1365-2893</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Amino Acid Substitution</term><term>Animals</term><term>Antigenic Variation</term><term>Antiviral Agents (therapeutic use)</term><term>Computational Biology</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Genetic Variation</term><term>Hepatitis B Surface Antigens (genetics)</term><term>Hepatitis B Surface Antigens (immunology)</term><term>Hepatitis B, Chronic (drug therapy)</term><term>Humans</term><term>Male</term><term>Mice, Inbred BALB C</term><term>Middle Aged</term><term>Mutant Proteins (genetics)</term><term>Mutant Proteins (immunology)</term><term>Nucleosides (therapeutic use)</term><term>Nucleotides (therapeutic use)</term><term>Sequence Analysis, DNA</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de séquence d'ADN</term><term>Animaux</term><term>Antigènes de surface du virus de l'hépatite B (génétique)</term><term>Antigènes de surface du virus de l'hépatite B (immunologie)</term><term>Antiviraux (usage thérapeutique)</term><term>Biologie informatique</term><term>Femelle</term><term>Humains</term><term>Hépatite B chronique (traitement médicamenteux)</term><term>Mâle</term><term>Nucléosides (usage thérapeutique)</term><term>Nucléotides (usage thérapeutique)</term><term>Protéines mutantes (génétique)</term><term>Protéines mutantes (immunologie)</term><term>Souris de lignée BALB C</term><term>Substitution d'acide aminé</term><term>Sujet âgé</term><term>Test ELISA</term><term>Variation des antigènes</term><term>Variation génétique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hepatitis B Surface Antigens</term><term>Mutant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Hepatitis B Surface Antigens</term><term>Mutant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>Nucleosides</term><term>Nucleotides</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Hepatitis B, Chronic</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes de surface du virus de l'hépatite B</term><term>Protéines mutantes</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes de surface du virus de l'hépatite B</term><term>Protéines mutantes</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Hépatite B chronique</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antiviraux</term><term>Nucléosides</term><term>Nucléotides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Amino Acid Substitution</term><term>Animals</term><term>Antigenic Variation</term><term>Computational Biology</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Genetic Variation</term><term>Humans</term><term>Male</term><term>Mice, Inbred BALB C</term><term>Middle Aged</term><term>Sequence Analysis, DNA</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de séquence d'ADN</term><term>Animaux</term><term>Biologie informatique</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Souris de lignée BALB C</term><term>Substitution d'acide aminé</term><term>Sujet âgé</term><term>Test ELISA</term><term>Variation des antigènes</term><term>Variation génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Inde</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Grand Est</li><li>Lorraine (région)</li><li>Rhône-Alpes</li></region><settlement><li>Lyon</li><li>Nancy</li><li>Vandœuvre-lès-Nancy</li></settlement><orgName><li>Université de Lorraine</li></orgName></list><tree><country name="France"><region name="Grand Est"><name sortKey="Velay, A" sort="Velay, A" uniqKey="Velay A" first="A" last="Velay">A. Velay</name></region><name sortKey="Bensenane, M" sort="Bensenane, M" uniqKey="Bensenane M" first="M" last="Bensenane">M. Bensenane</name><name sortKey="Bronowicki, J P" sort="Bronowicki, J P" uniqKey="Bronowicki J" first="J-P" last="Bronowicki">J-P Bronowicki</name><name sortKey="Combet, C" sort="Combet, C" uniqKey="Combet C" first="C" last="Combet">C. Combet</name><name sortKey="Eschlimann, M" sort="Eschlimann, M" uniqKey="Eschlimann M" first="M" last="Eschlimann">M. Eschlimann</name><name sortKey="Frippiat, J P" sort="Frippiat, J P" uniqKey="Frippiat J" first="J-P" last="Frippiat">J-P Frippiat</name><name sortKey="Goehringer, F" sort="Goehringer, F" uniqKey="Goehringer F" first="F" last="Goehringer">F. Goehringer</name><name sortKey="Jeulin, H" sort="Jeulin, H" uniqKey="Jeulin H" first="H" last="Jeulin">H. Jeulin</name><name sortKey="Malve, B" sort="Malve, B" uniqKey="Malve B" first="B" last="Malvé">B. Malvé</name><name sortKey="Schvoerer, E" sort="Schvoerer, E" uniqKey="Schvoerer E" first="E" last="Schvoerer">E. Schvoerer</name><name sortKey="Zoulim, F" sort="Zoulim, F" uniqKey="Zoulim F" first="F" last="Zoulim">F. Zoulim</name></country><country name="Inde"><noRegion><name sortKey="Abraham, P" sort="Abraham, P" uniqKey="Abraham P" first="P" last="Abraham">P. Abraham</name></noRegion><name sortKey="Ismail, A M" sort="Ismail, A M" uniqKey="Ismail A" first="A M" last="Ismail">A M Ismail</name></country><country name="Australie"><noRegion><name sortKey="Murray, J M" sort="Murray, J M" uniqKey="Murray J" first="J M" last="Murray">J M Murray</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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