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          Institute: MPI für Informatik     Collection: Computational Biology and Applied Algorithmics     Display Documents



ID: 618812.0, MPI für Informatik / Computational Biology and Applied Algorithmics
Role of hepatitis B virus genetic barrier in drug-resistance and immune-escape development
Authors:Svicher, Valentina; Cento, Valeria; Salpini, Romina; Mercurio, Fabio; Fraune, Maria; Beggel, Bastian; Han, Yue; Gori, Caterina; Wittkop, Linda; Bertoli, Ada; Micheli, Valeria; Gubertini, Guido; Longo, Roberta; Romano, Sara; Visca, Michela; Gallinaro, Valentina; Marino, Nicoletta; Mazzotta, Francesco; De Sanctis, Giuseppe Maria; Fleury, Hervè; Trimoulet, Pascale; Angelico, Mario; Cappiello, Giuseppina; Zhang, Xin Xin; Verheyen, Jens; Ceccherini-Silberstein, Francesca; Perno, Carlo Federico
Language:English
Date of Publication (YYYY-MM-DD):2011
Title of Journal:Digestive and Liver Disease
Volume:43
Issue / Number:12
Start Page:975
End Page:983
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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 virusreverse transcriptase/HBV surface antigen sequences from 555
drug-naïve patients and 2927 antiviraltreated 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. rtL80I/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 sG130N.
Vaccine-escape associated sT131N-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.
Last Change of the Resource (YYYY-MM-DD):2012-02-28
External Publication Status:published
Document Type:Article
Communicated by:Thomas Lengauer
Affiliations:MPI für Informatik/Computational Biology and Applied Algorithmics
Identifiers:LOCALID:C125673F004B2D7B-074828CB14111069C125796400478483-...
URL:http://dx.doi.org/10.1016/j.dld.2011.07.002
DOI:10.1016/j.dld.2011.07.002
ISSN:1590-8658
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