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Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA

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Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. / Lucifora, Julie; Xia, Yuchen; Reisinger, Florian; Zhang, Ke; Stadler, Daniela; Cheng, Xiaoming; Sprinzl, Martin F; Koppensteiner, Herwig; Makowska, Zuzanna; Volz, Tassilo; Remouchamps, Caroline; Chou, Wen-Min; Thasler, Wolfgang E; Hüser, Norbert; Durantel, David; Liang, T Jake; Münk, Carsten; Heim, Markus H; Browning, Jeffrey L; Dejardin, Emmanuel; Dandri, Maura; Schindler, Michael; Heikenwalder, Mathias; Protzer, Ulrike.

In: SCIENCE, Vol. 343, No. 6176, 14.03.2014, p. 1221-1228.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lucifora, J, Xia, Y, Reisinger, F, Zhang, K, Stadler, D, Cheng, X, Sprinzl, MF, Koppensteiner, H, Makowska, Z, Volz, T, Remouchamps, C, Chou, W-M, Thasler, WE, Hüser, N, Durantel, D, Liang, TJ, Münk, C, Heim, MH, Browning, JL, Dejardin, E, Dandri, M, Schindler, M, Heikenwalder, M & Protzer, U 2014, 'Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA', SCIENCE, vol. 343, no. 6176, pp. 1221-1228. https://doi.org/10.1126/science.1243462

APA

Lucifora, J., Xia, Y., Reisinger, F., Zhang, K., Stadler, D., Cheng, X., Sprinzl, M. F., Koppensteiner, H., Makowska, Z., Volz, T., Remouchamps, C., Chou, W-M., Thasler, W. E., Hüser, N., Durantel, D., Liang, T. J., Münk, C., Heim, M. H., Browning, J. L., ... Protzer, U. (2014). Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. SCIENCE, 343(6176), 1221-1228. https://doi.org/10.1126/science.1243462

Vancouver

Lucifora J, Xia Y, Reisinger F, Zhang K, Stadler D, Cheng X et al. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. SCIENCE. 2014 Mar 14;343(6176):1221-1228. https://doi.org/10.1126/science.1243462

Bibtex

@article{5a4b5efb1ec2415c80ca30c57c32baed,
title = "Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA",
abstract = "Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon-α treatment can clear HBV but is limited by systemic side effects. We describe how interferon-α can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-β receptor activation as a therapeutic alternative. Interferon-α and lymphotoxin-β receptor activation up-regulated APOBEC3A and APOBEC3B cytidine deaminases, respectively, in HBV-infected cells, primary hepatocytes, and human liver needle biopsies. HBV core protein mediated the interaction with nuclear cccDNA, resulting in cytidine deamination, apurinic/apyrimidinic site formation, and finally cccDNA degradation that prevented HBV reactivation. Genomic DNA was not affected. Thus, inducing nuclear deaminases-for example, by lymphotoxin-β receptor activation-allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.",
keywords = "Animals, Antibodies, Monoclonal, Antiviral Agents, Cell Line, Cell Nucleus, Cytidine, Cytidine Deaminase, DNA, Circular, DNA, Viral, Hepatitis B, Hepatitis B virus, Hepatocytes, Humans, Interferon-alpha, Liver, Lymphotoxin beta Receptor, Mice, SCID, Proteins, Up-Regulation",
author = "Julie Lucifora and Yuchen Xia and Florian Reisinger and Ke Zhang and Daniela Stadler and Xiaoming Cheng and Sprinzl, {Martin F} and Herwig Koppensteiner and Zuzanna Makowska and Tassilo Volz and Caroline Remouchamps and Wen-Min Chou and Thasler, {Wolfgang E} and Norbert H{\"u}ser and David Durantel and Liang, {T Jake} and Carsten M{\"u}nk and Heim, {Markus H} and Browning, {Jeffrey L} and Emmanuel Dejardin and Maura Dandri and Michael Schindler and Mathias Heikenwalder and Ulrike Protzer",
year = "2014",
month = mar,
day = "14",
doi = "10.1126/science.1243462",
language = "English",
volume = "343",
pages = "1221--1228",
journal = "SCIENCE",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6176",

}

RIS

TY - JOUR

T1 - Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA

AU - Lucifora, Julie

AU - Xia, Yuchen

AU - Reisinger, Florian

AU - Zhang, Ke

AU - Stadler, Daniela

AU - Cheng, Xiaoming

AU - Sprinzl, Martin F

AU - Koppensteiner, Herwig

AU - Makowska, Zuzanna

AU - Volz, Tassilo

AU - Remouchamps, Caroline

AU - Chou, Wen-Min

AU - Thasler, Wolfgang E

AU - Hüser, Norbert

AU - Durantel, David

AU - Liang, T Jake

AU - Münk, Carsten

AU - Heim, Markus H

AU - Browning, Jeffrey L

AU - Dejardin, Emmanuel

AU - Dandri, Maura

AU - Schindler, Michael

AU - Heikenwalder, Mathias

AU - Protzer, Ulrike

PY - 2014/3/14

Y1 - 2014/3/14

N2 - Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon-α treatment can clear HBV but is limited by systemic side effects. We describe how interferon-α can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-β receptor activation as a therapeutic alternative. Interferon-α and lymphotoxin-β receptor activation up-regulated APOBEC3A and APOBEC3B cytidine deaminases, respectively, in HBV-infected cells, primary hepatocytes, and human liver needle biopsies. HBV core protein mediated the interaction with nuclear cccDNA, resulting in cytidine deamination, apurinic/apyrimidinic site formation, and finally cccDNA degradation that prevented HBV reactivation. Genomic DNA was not affected. Thus, inducing nuclear deaminases-for example, by lymphotoxin-β receptor activation-allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.

AB - Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon-α treatment can clear HBV but is limited by systemic side effects. We describe how interferon-α can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-β receptor activation as a therapeutic alternative. Interferon-α and lymphotoxin-β receptor activation up-regulated APOBEC3A and APOBEC3B cytidine deaminases, respectively, in HBV-infected cells, primary hepatocytes, and human liver needle biopsies. HBV core protein mediated the interaction with nuclear cccDNA, resulting in cytidine deamination, apurinic/apyrimidinic site formation, and finally cccDNA degradation that prevented HBV reactivation. Genomic DNA was not affected. Thus, inducing nuclear deaminases-for example, by lymphotoxin-β receptor activation-allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.

KW - Animals

KW - Antibodies, Monoclonal

KW - Antiviral Agents

KW - Cell Line

KW - Cell Nucleus

KW - Cytidine

KW - Cytidine Deaminase

KW - DNA, Circular

KW - DNA, Viral

KW - Hepatitis B

KW - Hepatitis B virus

KW - Hepatocytes

KW - Humans

KW - Interferon-alpha

KW - Liver

KW - Lymphotoxin beta Receptor

KW - Mice, SCID

KW - Proteins

KW - Up-Regulation

U2 - 10.1126/science.1243462

DO - 10.1126/science.1243462

M3 - SCORING: Journal article

C2 - 24557838

VL - 343

SP - 1221

EP - 1228

JO - SCIENCE

JF - SCIENCE

SN - 0036-8075

IS - 6176

ER -