Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy
| العنوان: | Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy |
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| المؤلفون: | Marine Eschlimann, J. P. Bronowicki, John M. Murray, Priya Abraham, Brice Malve, Aurélie Velay, Jean-Pol Frippiat, Evelyne Schvoerer, M. Bensenane, Christophe Combet, François Goehringer, Fabien Zoulim, Hélène Jeulin, Ashrafali M. Ismail |
| المساهمون: | Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service d'Hépato-gastro-entérologie [CHRU Nancy], Christian Medical College & Hospital, University of New South Wales [Sydney] (UNSW), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | Journal of Viral Hepatitis Journal of Viral Hepatitis, Wiley-Blackwell, 2016, 23 (5), pp.387-398. ⟨10.1111/jvh.12498⟩ |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, HBsAg, Mutant, medicine.disease_cause, Persistence (computer science), 0302 clinical medicine, Medicine, S variability, Mice, Inbred BALB C, Nucleotides, virus diseases, Nucleosides, Middle Aged, Antigenic Variation, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Female, Hepatitis B Virus, Adult, Antigenicity, HBV preS, Enzyme-Linked Immunosorbent Assay, Anti-HBV treatment, Antiviral Agents, 03 medical and health sciences, Hepatitis B, Chronic, Virology, Genetic variation, Antigenic variation, Animals, Humans, Gene, Aged, Hepatitis B virus, Hepatitis B Surface Antigens, Hepatology, business.industry, Computational Biology, Genetic Variation, Sequence Analysis, DNA, digestive system diseases, 030104 developmental biology, Amino Acid Substitution, Immunology, Mutant Proteins, business |
| الوصف: | International audience; 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. |
| تدمد: | 1365-2893 1352-0504 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2e5b10d10123197832d113bfd0d7723eTest https://pubmed.ncbi.nlm.nih.gov/26742490Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....2e5b10d10123197832d113bfd0d7723e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652893 13520504 |
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