Role of hepatitis B virus genetic barrier in drug-resistance and immune-escape 
development

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

doi:10.1016/j.dld.2011.07.002

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Role of hepatitis B virus genetic barrier in drug-resistance and immune-escape development

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Beggel, Bastian
Computational Biology and Applied Algorithmics, MPI for Informatics, Max Planck Society;
International Max Planck Research School, MPI for Informatics, Max Planck Society;

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引用

Svicher, V., Cento, V., Salpini, R., Mercurio, F., Fraune, M., Beggel, B., Han, Y., Gori, C., Wittkop, L., Bertoli, A., Micheli, V., Gubertini, G., Longo, R., Romano, S., Visca, M., Gallinaro, V., Marino, N., Mazzotta, F., De Sanctis, G. M., Fleury, H., Trimoulet, P., Angelico, M., Cappiello, G., Zhang, X. X., Verheyen, J., Ceccherini-Silberstein, F., & Perno, C. F. (2011). Role of hepatitis B virus genetic barrier in drug-resistance and immune-escape development. Digestive and Liver Disease, 43(12), 975-983. doi:10.1016/j.dld.2011.07.002.

引用: https://hdl.handle.net/11858/00-001M-0000-0010-1372-0

要旨

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.