TY  - JOUR
AB  - BACKGROUND & AIMS: The sodium taurocholate cotransporting polypeptide (NTCP), the main hepatic uptake transporter of bile salts, is the docking receptor required for the HBV/HDV entry. However, the mechanism of NTCP-dependent internalization of HBV/HDV into hepatocytes is unclear. Thus, we investigated the contribution of post-translational modification of NTCP to transporter endocytosis and HBV infection. METHODS: NTCP ubiquitination was determined by immunoprecipitation of wild-type NTCP (NTCPWT). Lysine (K) residues in the C terminus were substituted by arginine (R) to identify ubiquitination sites. HepG2 cells overexpressing NTCP mutants were analyzed for protein levels, bile salt uptake activity, NTCP endocytosis, and HBV infectivity. The global ubiquitination inhibitor TAK-243 was used to study effects on uptake and HBV infection in NTCPWT-HepG2 and HepaRG cells. Sample sizes in the experiments were 3-10. RESULTS: NTCP was found to be ubiquitinated. Compared with NTCPWT, the NTCPK340R mutant showed reduced ubiquitination, indicating K340 as the main ubiquitination target. Furthermore, NTCPK340R had increased membrane abundance, which coincided with enhanced bile salt uptake (28.2 ± 5.3 vs. 74.4 ± 5.8 pmol; p <0.0001). Compared with NTCPWT, NTCPK340R endocytosis was strongly impaired (100 ± 47 vs. 42 ± 19%; p = 0.0079), whereas HBV-derived myr-preS1 peptide binding was increased (100 ± 33 vs. 220 ± 98%; p <0.0001). Compared with NTCPWT cells, HBV DNA content was strongly reduced in NTCPK340R cells (52.74 ± 26.23 vs. 7.22 ± 3.28%; p = 0.0022). In line with this, TAK-243 reduced cellular ubiquitination levels and increased bile salt uptake (48.65 ± 2.27 vs. 105.8 ± 4.12 pmol; p = 0.0286), while reducing HBV DNA content in HepG2 (100 ± 44 vs. 18 ± 13%; p <0.0001) and HepaRG cells (100 ± 24 vs. 65 ± 6%; p = 0.0483). CONCLUSIONS: K340 is essential for NTCP ubiquitination. Inhibiting ubiquitination impaired NTCP endocytosis and reduced HBV infection, confirming that NTCP-mediated endocytosis is critical for HBV hepatic entry. IMPACT AND IMPLICATIONS: This study contributes to elucidating the process of how HBV enters hepatocytes, which is largely elusive. NTCP was found not only to be required for the binding of HBV to hepatocytes, but also to have a crucial role in hepatic internalization of HBV. In addition, a K at position 340 was identified as the main ubiquitination target of NTCP; ubiquitination-mediated endocytosis of NTCP at this position is likely to be the mechanism regulating HBV internalization. Thus, interfering with NTCP ubiquitination could provide a novel means to reduce HBV infection.
AU  - Appelman, M.D.*
AU  - Nguyen, T.A.*
AU  - Oswald, A.
AU  - Lucko, A.M.
AU  - Paulusma, C.C.*
AU  - Protzer, U.
AU  - van de Graaf, S.F.J.*
C1  - 75835
C2  - 58134
TI  - NTCP ubiquitination enables HBV infection.
JO  - JHEP Rep.
VL  - 7
IS  - 11
PY  - 2025
SN  - 2589-5559
ER  - 

TY  - JOUR
AB  - BACKGROUND & AIMS: Inoperable hepatocellular carcinoma (HCC) can be treated by stereotactic body radiotherapy. However, carbon ion radiotherapy (CIRT) is more effective for sparing non-tumorous liver. High linear energy transfer could promote therapy efficacy. Japanese and Chinese studies on hypofractionated CIRT have yielded excellent results. Because of different radiobiological models and the different etiological spectrum of HCC, applicability of these results to European cohorts and centers remains questionable. The aim of this prospective study was to assess safety and efficacy and to determine the optimal dose of CIRT with active raster scanning based on the local effect model (LEM) I. METHODS: CIRT was performed every other day in four fractions with relative biological effectiveness (RBE)-weighted fraction doses of 8.1-10.5 Gy (total doses 32.4-42.0 Gy [RBE]). Dose escalation was performed in five dose levels with at least three patients each. The primary endpoint was acute toxicity after 4 weeks. RESULTS: Twenty patients received CIRT (median age 74.7 years, n = 16 with liver cirrhosis, Child-Pugh scores [CP] A5 [n = 10], A6 [n = 4], B8 [n = 1], and B9 [n = 1]). Median follow up was 23 months. No dose-limiting toxicities and no toxicities exceeding grade II occurred, except one grade III gamma-glutamyltransferase elevation 12 months after CIRT, synchronous to out-of-field hepatic progression. During 12 months after CIRT, no CP elevation occurred. The highest dose level could be applied safely. No local recurrence developed during follow up. The objective response rate was 80%. Median overall survival was 30.8 months (1/2/3 years: 75%/64%/22%). Median progression-free survival was 20.9 months (1/2/3 years: 59%/43%/43%). Intrahepatic progression outside of the CIRT target volume was the most frequent pattern of progression. CONCLUSIONS: CIRT of HCC yields excellent local control without dose-limiting toxicity. IMPACT AND IMPLICATIONS: To date, safety and efficacy of carbon ion radiotherapy for hepatocellular carcinoma have only been evaluated prospectively in Japanese and Chinese studies. The optimal dose and fractionation when using the local effect model for radiotherapy planning are unknown. The results are of particular interest for European and American particle therapy centers, but also of relevance for all specialists involved in the treatment and care of patients with hepatocellular carcinoma, as we present the first prospective data on carbon ion radiotherapy in hepatocellular carcinoma outside of Asia. The excellent local control should encourage further use of carbon ion radiotherapy for hepatocellular carcinoma and design of randomized controlled trials. CLINICAL TRIALS REGISTRATION: The study is registered at ClinicalTrials.gov (NCT01167374).
AU  - Hoegen-Saßmannshausen, P.*
AU  - Naumann, P.*
AU  - Hoffmeister-Wittmann, P.*
AU  - Ben Harrabi, S.*
AU  - Seidensaal, K.*
AU  - Weykamp, F.*
AU  - Mielke, T.*
AU  - Ellerbrock, M.*
AU  - Habermehl, D.*
AU  - Springfeld, C.*
AU  - Dill, M.T.*
AU  - Longerich, T.*
AU  - Schirmacher, P.*
AU  - Mehrabi, A.*
AU  - Chang, D.H.*
AU  - Hörner-Rieber, J.*
AU  - Jäkel, O.*
AU  - Haberer, T.*
AU  - Combs, S.E.
AU  - Debus, J.*
AU  - Herfarth, K.*
AU  - Liermann, J.*
C1  - 70642
C2  - 55793
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - Carbon ion radiotherapy of hepatocellular carcinoma provides excellent local control: The prospective phase I PROMETHEUS trial.
JO  - JHEP Rep.
VL  - 6
IS  - 6
PB  - Elsevier
PY  - 2024
SN  - 2589-5559
ER  - 

TY  - JOUR
AB  - BACKGROUND & AIMS: Although most hepatocellular carcinoma (HCC) cases are driven by hepatitis and cirrhosis, a subset of patients with chronic hepatitis B develop HCC in the absence of advanced liver disease, indicating the oncogenic potential of hepatitis B virus (HBV). We investigated the role of HBV transcripts and proteins on HCC development in the absence of inflammation in HBV-transgenic mice. METHODS: HBV-transgenic mice replicating HBV and expressing all HBV proteins from a single integrated 1.3-fold HBV genome in the presence or absence of wild-type HBx (HBV1.3/HBVxfs) were analyzed. Flow cytometry, molecular, histological and in vitro analyses using human cell lines were performed. Hepatocyte-specific Stat3- and Socs3-knockout was analyzed in HBV1.3 mice. RESULTS: Approximately 38% of HBV1.3 mice developed liver tumors. Protein expression patterns, histology, and mutational landscape analyses indicated that tumors resembled human HCC. HBV1.3 mice showed no signs of active hepatitis, except STAT3 activation, up to the time point of HCC development. HBV-RNAs covering HBx sequence, 3.5-kb HBV RNA and HBx-protein were detected in HCC tissue. Interestingly, HBVxfs mice expressing all HBV proteins except a C-terminally truncated HBx (without the ability to bind DNA damage binding protein 1) showed reduced signs of DNA damage response and had a significantly reduced HCC incidence. Importantly, intercrossing HBV1.3 mice with a hepatocyte-specific STAT3-knockout abrogated HCC development. CONCLUSIONS: Expression of HBV-proteins is sufficient to cause HCC in the absence of detectable inflammation. This indicates the oncogenic potential of HBV and in particular HBx. In our model, HBV-driven HCC was STAT3 dependent. Our study highlights the immediate oncogenic potential of HBV, challenging the idea of a benign highly replicative phase of HBV infection and indicating the necessity for an HBV 'cure'. IMPACT AND IMPLICATIONS: Although most HCC cases in patients with chronic HBV infection occur after a sequence of liver damage and fibrosis, a subset of patients develops HCC without any signs of advanced liver damage. We demonstrate that the expression of all viral transcripts in HBV-transgenic mice suffices to induce HCC development independent of inflammation and fibrosis. These data indicate the direct oncogenic effects of HBV and emphasize the idea of early antiviral treatment in the 'immune-tolerant' phase (HBeAg-positive chronic HBV infection).
AU  - Ringelhan, M.*
AU  - Schuehle, S.*
AU  - van de Klundert, M.
AU  - Kotsiliti, E.*
AU  - Plissonnier, M.L.*
AU  - Faure-Dupuy, S.*
AU  - Riedl, T.*
AU  - Lange, S.*
AU  - Wisskirchen, K.
AU  - Thiele, F.
AU  - Cheng, C.-C.
AU  - Yuan, D.T.
AU  - Leone, V.
AU  - Schmidt, R.*
AU  - Hünergard, J.
AU  - Geisler, F.*
AU  - Unger, K.
AU  - Algül, H.*
AU  - Schmid, R.M.*
AU  - Rad, R.*
AU  - Wedemeyer, H.*
AU  - Levrero, M.*
AU  - Protzer, U.
AU  - Heikenwälder, M.
C1  - 71753
C2  - 56427
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - HBV-related HCC development in mice is STAT3 dependent and indicates an oncogenic effect of HBx.
JO  - JHEP Rep.
VL  - 6
IS  - 10
PB  - Elsevier
PY  - 2024
SN  - 2589-5559
ER  - 

TY  - JOUR
AB  - Background & Aims: Particulate hepatitis B core antigen (HBcoreAg) is a potent immunogen used as a vaccine carrier
      platform. HBcoreAg produced in E. coli encapsidates random bacterial RNA (bRNA). Using the heterologous protein-prime,
      viral-vector-boost therapeutic hepatitis B vaccine TherVacB, we compared the properties of different HBcoreAg forms. We
      explored how the content of HBcoreAg modulates antigen stability, immunogenicity, and antiviral efficacy.
      Methods: bRNA was removed from HBcoreAg by capsid disassembly, followed by reassembly in the absence or presence of
      specific nucleic acid-based adjuvants poly I:C or CpG. The morphology and structure of empty, bRNA-containing and
      adjuvant-loaded HBcoreAg were monitored by electron microscopy and nuclear magnetic resonance spectroscopy. Empty, bRNA-containing or adjuvant-loaded HBcoreAg were applied together with HBsAg and with or without nucleic acid-based external adjuvants within the TherVacB regimen in both wild-type and HBV-carrier mice. Results: While HBcoreAg retained its structure upon bRNA removal, its stability and immunogenicity decreased significantly. Loading HBcoreAg with nucleic acid-based adjuvants re-established stability of the capsid-like antigen. Immunization with poly I:C- or CpG-loaded HBcoreAg induced high antibody titers against co-administered HBsAg. When applied within the
      TherVacB regimen, they activated vigorous HBcoreAg- and HBsAg-specific T-cell responses in wild-type and HBV-carrier mice, requiring a significantly lower dose of adjuvant compared to externally added adjuvant. Finally, immunization with adjuvant-loaded HBcoreAg mixed with HBsAg led to long-term control of persistent HBV replication in the HBV-carrier mice. Conclusion: Adjuvant-loaded HBcoreAg retained capsid integrity and stability, was as immunogenic in vivo as externally adjuvanted HBcoreAg, requiring lower adjuvant levels, and supported immunity against co-administered, non-adjuvanted
      HBsAg. Thus, adjuvant-loaded HBcoreAg represents a promising novel platform for vaccine development. Impact and implications: Hepatitis B core antigen (HBcoreAg) recapitulates the capsid of the HBV that hosts the viral genome. Produced recombinantly, it is not infectious but emerges as a potent immunogen in vaccine development. In this
      preclinical study, we show that loading HBcoreAg with defined nucleic-acid-based adjuvants on the one hand stabilizes the HBcoreAg with standardized capsid content and, on the other hand, efficiently promotes the immunity of HBcoreAg and a co-
      administered antigen, allowing for reduced adjuvant doses. Therefore, adjuvant-loaded HBcoreAg not only serves as an encouraging option for therapeutic hepatitis B vaccines, but could also act as an efficient adjuvant delivery system for other types of vaccine.
AU  - Su, J.
AU  - Harati Taji, Z.
AU  - Kosinska, A.
AU  - Ates Öz, E.
AU  - Xie, Z.
AU  - Bielytskyi, P.
AU  - Shein, M.
AU  - Hagen, P.
AU  - Esmaeili, S.
AU  - Steiger, K.*
AU  - Protzer, U.
AU  - Schütz, A.K.
C1  - 70082
C2  - 55011
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - Introducing adjuvant-loaded particulate hepatitis B core antigen as an alternative therapeutic hepatitis B vaccine component.
JO  - JHEP Rep.
VL  - 6
IS  - 4
PB  - Elsevier
PY  - 2024
SN  - 2589-5559
ER  - 

TY  - JOUR
AB  - Background & Aims: Mcl-1, an antiapoptotic protein overexpressed in many tumours, including hepatocellular carcinoma (HCC), represents a promising target for cancer treatment. Although Mcl-1 non-apoptotic roles might critically influence the therapeutic potential of Mcl-1 inhibitors, these functions remain poorly understood. We aimed to investigate the effects of hepatic Mcl-1 deficiency (Mcl-1Δhep) on hepatocyte ploidy and cell cycle in murine liver in vivo and the possible implications on HCC. Methods: Livers of young Mcl-1Δhep and wild-type (WT) mice were analysed for ploidy profile, mitotic figures, in situ chromosome segregation, gene set enrichment analysis and were subjected to two-thirds partial hepatectomy to assess Mcl-1 deficiency effect on cell cycle progression in vivo. Mcl-1Δhep tumours in older mice were analysed for ploidy profile, chromosomal instability, and mutational signatures via whole exome sequencing. Results: In young mice, Mcl-1 deficiency leads to nuclear polyploidy and to high rates of mitotic errors with abnormal spindle figures and chromosome mis-segregation along with a prolonged spindle assembly checkpoint activation signature. Chromosomal instability and altered ploidy profile are observed in Mcl-1Δhep tumours of old mice as well as a characteristic mutational signature of currently unknown aetiology. Conclusions: Our study suggests novel non-apoptotic effects of Mcl-1 deficiency on nuclear ploidy, mitotic regulation, and chromosomal segregation in hepatocytes in vivo. In addition, the Mcl-1 deficiency characteristic mutational signature might reflect mitotic issues. These results are of importance to consider when developing anti-Mcl-1 therapies to treat cancer. Impact and implications: Although Mcl-1 inhibitors represent promising hepatocellular carcinoma treatment, the still poorly understood non-apoptotic roles of Mcl-1 might compromise their successful clinical application. Our study shows that Mcl-1 deficiency leads to nuclear polyploidy, mitotic errors, and aberrant chromosomal segregation in hepatocytes in vivo, whereas hepatocellular tumours spontaneously induced by Mcl-1 deficiency exhibit chromosomal instability and a mutational signature potentially reflecting mitotic issues. These results have potential implications for the development of anti-Mcl-1 therapies to treat hepatocellular carcinoma, especially as hyperproliferative liver is a clinically relevant situation.
AU  - Clerbaux, L.A.*
AU  - Cordier, P.*
AU  - Desboeufs, N.*
AU  - Unger, K.
AU  - Leary, P.*
AU  - Semere, G.*
AU  - Boege, Y.*
AU  - Chan, L.K.*
AU  - Desdouets, C.*
AU  - Lopes, M.*
AU  - Weber, A.*
C1  - 68345
C2  - 54749
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - Mcl-1 deficiency in murine livers leads to nuclear polyploidisation and mitotic errors: Implications for hepatocellular carcinoma.
JO  - JHEP Rep.
VL  - 5
IS  - 10
PB  - Elsevier
PY  - 2023
SN  - 2589-5559
ER  - 

TY  - JOUR
AB  - Background & Aims: Induction of potent, HBV-specific immune responses is crucial to control and finally cure HBV. The therapeutic hepatitis B vaccine TherVacB combines protein priming with a Modified Vaccinia virus Ankara (MVA)-vector boost to break immune tolerance in chronic HBV infection. Particulate protein and vector vaccine components, however, require a constant cooling chain for storage and transport, posing logistic and financial challenges to vaccine applications. We aimed to identify an optimal formulation to maintain stability and immunogenicity of the protein and vector components of the vaccine using a systematic approach. Methods: We used stabilizing amino acid (SAA)-based formulations to stabilize HBsAg and HBV core particles (HBcAg), and the MVA-vector. We then investigated the effect of lyophilization and short- and long-term high-temperature storage on their integrity. Immunogenicity and safety of the formulated vaccine was validated in HBV-naïve and adeno-associated virus (AAV)-HBV-infected mice. Results: In vitro analysis proved the vaccine's stability against thermal stress during lyophilization and the long-term stability of SAA-formulated HBsAg, HBcAg and MVA during thermal stress at 40 °C for 3 months and at 25 °C for 12 months. Vaccination of HBV-naïve and AAV-HBV-infected mice demonstrated that the stabilized vaccine was well tolerated and able to brake immune tolerance established in AAV-HBV mice as efficiently as vaccine components constantly stored at 4 °C/−80 °C. Even after long-term exposure to elevated temperatures, stabilized TherVacB induced high titre HBV-specific antibodies and strong CD8+ T-cell responses, resulting in anti-HBs seroconversion and strong suppression of the virus in HBV-replicating mice. Conclusion: SAA-formulation resulted in highly functional and thermostable HBsAg, HBcAg and MVA vaccine components. This will facilitate global vaccine application without the need for cooling chains and is important for the development of prophylactic as well as therapeutic vaccines supporting vaccination campaigns worldwide. Impact and implications: Therapeutic vaccination is a promising therapeutic option for chronic hepatitis B that may enable its cure. However, its application requires functional cooling chains during transport and storage that can hardly be guaranteed in many countries with high demand. In this study, the authors developed thermostable vaccine components that are well tolerated and that induce immune responses and control the virus in preclinical mouse models, even after long-term exposure to high surrounding temperatures. This will lower costs and ease application of a therapeutic vaccine and thus be beneficial for the many people affected by hepatitis B around the world.
AU  - Sacherl, J.
AU  - Kosinska, A.
AU  - Kemter, K.*
AU  - Kächele, M.
AU  - Laumen, S.C.
AU  - Kerth, H.A.
AU  - Öz, E.A.
AU  - Wolff, L.S.
AU  - Su, J.
AU  - Essbauer, S.*
AU  - Sutter, G.*
AU  - Scholz, M.*
AU  - Singethan, K.
AU  - Altrichter, J.*
AU  - Protzer, U.
C1  - 67112
C2  - 53481
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - Efficient stabilization of therapeutic hepatitis B vaccine components by amino-acid formulation maintains its potential to break immune tolerance.
JO  - JHEP Rep.
VL  - 5
IS  - 2
PB  - Elsevier
PY  - 2023
SN  - 2589-5559
ER  - 

TY  - JOUR
AB  - Background & Aims: The chronicity of HBV (and resultant liver disease) is determined by intrahepatic persistence of the HBV covalently closed circular DNA (cccDNA), an episomal form that encodes all viral transcripts. Therefore, cccDNA is a key target for new treatments, with the ultimate therapeutic aim being its complete elimination. Although established cccDNA molecules are known to be stable in resting hepatocytes, we aimed to understand their fate in dividing cells using in vitro models. Methods: We infected HepG2-NTCP and HepaRG-NTCP cells with HBV and induced mitosis by passaging cells. We measured cccDNA copy number (by precise PCR assays) and HBV-expressing cells (by immunofluorescence) with wild-type HBV. We used reporter viruses expressing luciferase or RFP to track number of HBV-expressing cells over time after mitosis induction using luciferase assays and live imaging, respectively. Results: In all cases, we observed dramatic reductions in cccDNA levels, HBV-positive cell numbers, and cccDNA-dependent protein expression after each round of cell mitosis. The rates of reduction were highly consistent with mathematical models of a complete cccDNA loss in (as opposed to dilution into) daughter cells. Conclusions: Our results are concordant with previous animal models of HBV infection and show that HBV persistence can be efficiently overcome by inducing cell mitosis. These results support therapeutic approaches that induce liver turnover (e.g. immune modulators) in addition to direct-acting antiviral therapies to achieve hepatitis B cure. Lay summary: Chronic hepatitis B affects 300 million people (killing 884,000 per year) and is incurable. To cure it, we need to clear the HBV genome from the liver. In this study, we looked at how the virus behaves after a cell divides. We found that it completely clears the virus, making 2 new uninfected cells. Our work informs new approaches to develop cures for chronic hepatitis B infections.
AU  - Tu, T.*
AU  - Zehnder, B.*
AU  - Wettengel, J.M.
AU  - Zhang, H.*
AU  - Coulter, S.*
AU  - Ho, V.*
AU  - Douglas, M.W.*
AU  - Protzer, U.
AU  - George, J.*
AU  - Urban, S.*
C1  - 65803
C2  - 52914
TI  - Mitosis of hepatitis B virus-infected cells in vitro results in uninfected daughter cells.
JO  - JHEP Rep.
VL  - 4
IS  - 9
PY  - 2022
SN  - 2589-5559
ER  - 

TY  - JOUR
AB  - Background & Aims: Immune-mediated induction of cytidine deaminase APOBEC3B (A3B) expression leads to HBV covalently closed circular DNA (cccDNA) decay. Here, we aimed to decipher the signalling pathway(s) and regulatory mechanism(s) involved in A3B induction and related HBV control. Methods: Differentiated HepaRG cells (dHepaRG) knocked-down for NF-κB signalling components, transfected with siRNA or micro RNAs (miRNA), and primary human hepatocytes ± HBV or HBVΔX or HBV-RFP, were treated with lymphotoxin beta receptor (LTβR)-agonist (BS1). The biological outcomes were analysed by reverse transcriptase-qPCR, immunoblotting, luciferase activity, chromatin immune precipitation, electrophoretic mobility-shift assay, targeted-bisulfite-, miRNA-, RNA-, genome-sequencing, and mass-spectrometry. Results: We found that canonical and non-canonical NF-κB signalling pathways are mandatory for A3B induction and anti-HBV effects. The degree of immune-mediated A3B production is independent of A3B promoter demethylation but is controlled post-transcriptionally by the miRNA 138-5p expression (hsa-miR-138-5p), promoting A3B mRNA decay. Hsa-miR-138-5p over-expression reduced A3B levels and its antiviral effects. Of note, established infection inhibited BS1-induced A3B expression through epigenetic modulation of A3B promoter. Twelve days of treatment with a LTβR-specific agonist BS1 is sufficient to reduce the cccDNA pool by 80% without inducing significant damages to a subset of cancer-related host genes. Interestingly, the A3B-mediated effect on HBV is independent of the transcriptional activity of cccDNA as well as on rcDNA synthesis. Conclusions: Altogether, A3B represents the only described enzyme to target both transcriptionally active and inactive cccDNA. Thus, inhibiting hsa-miR-138-5p expression should be considered in the combinatorial design of new therapies against HBV, especially in the context of immune-mediated A3B induction. Lay summary: Immune-mediated induction of cytidine deaminase APOBEC3B is transcriptionally regulated by NF-κB signalling and post-transcriptionally downregulated by hsa-miR-138-5p expression, leading to cccDNA decay. Timely controlled APOBEC3B-mediated cccDNA decay occurs independently of cccDNA transcriptional activity and without damage to a subset of cancer-related genes. Thus, APOBEC3B-mediated cccDNA decay could offer an efficient therapeutic alternative to target hepatitis B virus chronic infection.
AU  - Faure-Dupuy, S.*
AU  - Riedl, T.*
AU  - Rolland, M.*
AU  - Hizir, Z.*
AU  - Reisinger, F.
AU  - Neuhaus, K.*
AU  - Schuehle, S.*
AU  - Remouchamps, C.*
AU  - Gillet, N.*
AU  - Schönung, M.*
AU  - Stadler, M.*
AU  - Wettengel, J.M.
AU  - Barnault, R.*
AU  - Parent, R.*
AU  - Schuster, L.C.*
AU  - Farhat, R.*
AU  - Prokosch, S.*
AU  - Leuchtenberger, C.*
AU  - Öllinger, R.*
AU  - Engleitner, T.*
AU  - Rippe, K.*
AU  - Rad, R.*
AU  - Unger, K.
AU  - Tscharahganeh, D.*
AU  - Lipka, D.B.*
AU  - Protzer, U.
AU  - Durantel, D.*
AU  - Lucifora, J.*
AU  - Dejardin, E.*
AU  - Heikenwälder, M.*
C1  - 63440
C2  - 51535
TI  - Control of APOBEC3B induction and cccDNA decay by NF-κB and miR-138-5p.
JO  - JHEP Rep.
VL  - 3
IS  - 6
PY  - 2021
SN  - 2589-5559
ER  -