Universität zu Köln

Svicher, Valentina, Cento, Valeria ORCID: 0000-0002-3272-4252, Salpini, Romina ORCID: 0000-0002-2488-2082, Mercurio, Fabio, Fraune, Maria, Beggel, Bastian, Han, Yue, Gori, Caterina, Wittkop, Linda ORCID: 0000-0003-2403-0960, Bertoli, Ada, Micheli, Valeria ORCID: 0000-0001-5629-3875, Gubertini, Guido, Longo, Roberta, Romano, Sara, Visca, Michela, Gallinaro, Valentina, Marino, Nicoletta, Mazzotta, Francesco, De Sanctis, Giuseppe Maria, Fleury, Herve, Trimoulet, Pascale, Angelico, Mario, Cappiello, Giuseppina, Zhang, Xin Xin, Verheyen, Jens, Ceccherini-Silberstein, Francesca and Perno, Carlo Federico (2011). Role of hepatitis B virus genetic barrier in drug-resistance and immune-escape development. Dig. Liver Dis., 43 (12). S. 975 - 984. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1590-8658

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Abstract

Background: Impact of hepatitis B virus genetic barrier, defined as the number and type of nucleotide substitutions required to overcome drug/immune selective pressure, on drug-resistance/immune-escape development is unknown. Methods: Genetic barrier was calculated according to Van de Vijver (2006) in 3482 hepatitis B virus-reverse transcriptase/HBV surface antigen sequences from 555 drug-naive patients and 2927 antiviral-treated patients infected with hepatitis B virus genotypes A-G. Results: Despite high natural variability, genetic barrier for drug-resistance development is identical amongst hepatitis B virus genotypes, but varies according to drug-resistance mutation type. Highest genetic barrier is found for secondary/compensatory mutations (e.g. rtL801/V-rtL180M-rtV173L), whilst most primary mutations (including rtM204V-rtA181T/V-rtI169T-rtA194T) are associated with low genetic barrier. An exception is rtM204I, which can derive from a transition or a transversion. Genotypes A and G are more prone to develop immune/diagnostic-escape mutations sT114R and 5G130N. Vaccine-escape associated 5T131N-mutation is a natural polymorphism in both A and G genotypes. Conclusion: Genetic barrier and reverse transcriptase/HBV surface antigen overlapping can synergistically influence hepatitis B virus drug-resistance/immune-escape development. The different immune-escape potential of specific hepatitis B virus genotypes could have important clinical consequences in terms of disease progression, vaccine strategies and correct HBV surface antigen detection. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Svicher, Valentina UNSPECIFIED UNSPECIFIED UNSPECIFIED Cento, Valeria UNSPECIFIED orcid.org/0000-0002-3272-4252 UNSPECIFIED Salpini, Romina UNSPECIFIED orcid.org/0000-0002-2488-2082 UNSPECIFIED Mercurio, Fabio UNSPECIFIED UNSPECIFIED UNSPECIFIED Fraune, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Beggel, Bastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Han, Yue UNSPECIFIED UNSPECIFIED UNSPECIFIED Gori, Caterina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittkop, Linda UNSPECIFIED orcid.org/0000-0003-2403-0960 UNSPECIFIED Bertoli, Ada UNSPECIFIED UNSPECIFIED UNSPECIFIED Micheli, Valeria UNSPECIFIED orcid.org/0000-0001-5629-3875 UNSPECIFIED Gubertini, Guido UNSPECIFIED UNSPECIFIED UNSPECIFIED Longo, Roberta UNSPECIFIED UNSPECIFIED UNSPECIFIED Romano, Sara UNSPECIFIED UNSPECIFIED UNSPECIFIED Visca, Michela UNSPECIFIED UNSPECIFIED UNSPECIFIED Gallinaro, Valentina UNSPECIFIED UNSPECIFIED UNSPECIFIED Marino, Nicoletta UNSPECIFIED UNSPECIFIED UNSPECIFIED Mazzotta, Francesco UNSPECIFIED UNSPECIFIED UNSPECIFIED De Sanctis, Giuseppe Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Fleury, Herve UNSPECIFIED UNSPECIFIED UNSPECIFIED Trimoulet, Pascale UNSPECIFIED UNSPECIFIED UNSPECIFIED Angelico, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Cappiello, Giuseppina UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Xin Xin UNSPECIFIED UNSPECIFIED UNSPECIFIED Verheyen, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Ceccherini-Silberstein, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Perno, Carlo Federico UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-484793
DOI:	10.1016/j.dld.2011.07.002
Journal or Publication Title:	Dig. Liver Dis.
Volume:	43
Number:	12
Page Range:	S. 975 - 984
Date:	2011
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1590-8658
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AMINO-ACID SUBSTITUTIONS; SURFACE-ANTIGEN; HEPATOCELLULAR-CARCINOMA; ANTIVIRAL RESISTANCE; REDUCED ANTIGENICITY; LAMIVUDINE THERAPY; CLINICAL-RELEVANCE; GENOTYPE-A; POLYMERASE; MUTATION Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48479