{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:11:13Z","timestamp":1779311473199,"version":"3.51.4"},"reference-count":64,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["16-15-10426"],"award-info":[{"award-number":["16-15-10426"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Chronic hepatitis B virus infection (CHB) caused by the hepatitis B virus (HBV) is one of the most common viral infections in the world. Reactivation of HBV infection is a life-threatening condition observed in patients with CHB receiving chemotherapy or other medications. Although HBV reactivation is commonly attributed to immune suppression, other factors have long been suspected to play a role, including intracellular signaling activated in response to DNA damage. We investigated the effects of DNA-damaging factors (doxorubicin and hydrogen peroxide) on HBV reactivation\/replication and the consequent DNA-damage response. Dose-dependent activation of HBV replication was observed in response to doxorubicin and hydrogen peroxide which was associated with a marked elevation in the mRNA levels of ataxia-telangiectasia mutated (ATM) and ATM- and RAD3-related (ATR) kinases. Downregulation of ATM or ATR expression by shRNAs substantially reduced the levels of HBV RNAs and DNA. In contrast, transcriptional activation of ATM or ATR using CRISPRa significantly increased HBV replication. We conclude that ATM and ATR are essential for HBV replication. Furthermore, DNA damage leading to the activation of ATM and ATR transcription, results in the reactivation of HBV replication.<\/jats:p>","DOI":"10.3390\/v11110997","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T06:33:29Z","timestamp":1572503609000},"page":"997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage"],"prefix":"10.3390","volume":"11","author":[{"given":"Anastasiya","family":"Kostyusheva","sequence":"first","affiliation":[{"name":"National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, Moscow 127994, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Brezgin","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, Moscow 127994, Russia"},{"name":"Institute of Immunology, Federal Medical Biological Agency, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Bayurova","sequence":"additional","affiliation":[{"name":"NF Gamaleya Research Center of Epidemiology and Microbiology, Moscow 123098, Russia"},{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow 108819, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4551-7535","authenticated-orcid":false,"given":"Ilya","family":"Gordeychuk","sequence":"additional","affiliation":[{"name":"NF Gamaleya Research Center of Epidemiology and Microbiology, Moscow 123098, Russia"},{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow 108819, Russia"},{"name":"Sechenov First Moscow State Medical University, Moscow 119146, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-2254","authenticated-orcid":false,"given":"Maria","family":"Isaguliants","sequence":"additional","affiliation":[{"name":"NF Gamaleya Research Center of Epidemiology and Microbiology, Moscow 123098, Russia"},{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow 108819, Russia"},{"name":"Department of Pathology, Riga Stradins University, LV-1007 Riga, Latvia"},{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7445-8044","authenticated-orcid":false,"given":"Irina","family":"Goptar","sequence":"additional","affiliation":[{"name":"Izmerov Research Institute of Occupational Health, Gene Engineering and Biotechnology, Moscow 105275, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2304-7787","authenticated-orcid":false,"given":"Felix","family":"Urusov","sequence":"additional","affiliation":[{"name":"Izmerov Research Institute of Occupational Health, Gene Engineering and Biotechnology, Moscow 105275, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6279-2101","authenticated-orcid":false,"given":"Anastasiya","family":"Nikiforova","sequence":"additional","affiliation":[{"name":"Izmerov Research Institute of Occupational Health, Gene Engineering and Biotechnology, Moscow 105275, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Volchkova","sequence":"additional","affiliation":[{"name":"Sechenov First Moscow State Medical University, Moscow 119146, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1851-7441","authenticated-orcid":false,"given":"Dmitry","family":"Kostyushev","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, Moscow 127994, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-9293","authenticated-orcid":false,"given":"Vladimir","family":"Chulanov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, Moscow 127994, Russia"},{"name":"Sechenov First Moscow State Medical University, Moscow 119146, Russia"},{"name":"Central Research Institute of Epidemiology, Moscow 111123, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1016\/S0140-6736(18)31865-8","article-title":"Chronic Hepatitis B Virus Infection","volume":"392","author":"Seto","year":"2018","journal-title":"Lancet"},{"key":"ref_2","unstructured":"(2017). World Health Organization. Global Hepatitis Report, 2017, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.jhep.2015.06.006","article-title":"The Long-Term Benefits of Nucleos(t)Ide Analogs in Compensated HBV Cirrhotic Patients with No or Small Esophageal Varices: A 12-Year Prospective Cohort Study","volume":"63","author":"Lampertico","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/0016-5085(91)90599-G","article-title":"Reactivation of Hepatitis B Virus Replication in Patients Receiving Cytotoxic Therapy. Report of a Prospective Study","volume":"100","author":"Lok","year":"1991","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1053\/j.gastro.2017.02.009","article-title":"Hepatitis B Reactivation Associated With Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions","volume":"152","author":"Loomba","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S306","DOI":"10.1093\/cid\/ciw043","article-title":"Hepatitis B Virus Reactivation in the Setting of Cancer Chemotherapy and Other Immunosuppressive Drug Therapy","volume":"62","author":"Gonzalez","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1111\/j.1365-2133.2006.07451.x","article-title":"Late Lethal Hepatitis B Virus Reactivation after Rituximab Treatment of Low-Grade Cutaneous B-Cell Lymphoma","volume":"155","author":"Perceau","year":"2006","journal-title":"Br. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1111\/j.1478-3231.2010.02238.x","article-title":"Adalimumab-Induced Lethal Hepatitis B Virus Reactivation in an HBsAg-Negative Patient with Clinically Resolved Hepatitis B Virus Infection","volume":"30","author":"Matsumoto","year":"2010","journal-title":"Liver Int."},{"key":"ref_9","first-page":"3035","article-title":"Doxorubicin Activates Hepatitis B Virus (HBV) Replication in HBV-Harboring Hepatoblastoma Cells. A Possible Novel Mechanism of HBV Reactivation in HBV Carriers Receiving Systemic Chemotherapy","volume":"24","author":"Hsu","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1002\/cam4.1468","article-title":"RFX1 Participates in Doxorubicin-Induced Hepatitis B Virus Reactivation","volume":"7","author":"Wang","year":"2018","journal-title":"Cancer Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chen, Y.-F., Chong, C.-L., Wu, Y.-C., Wang, Y.-L., Tsai, K.-N., Kuo, T.-M., Hong, M.-H., Hu, C.-P., Chen, M.-L., and Chou, Y.-C. (2015). Doxorubicin Activates Hepatitis B Virus Replication by Elevation of P21 (Waf1\/Cip1) and C\/EBP\u03b1 Expression. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131743"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.3748\/wjg.v21.i5.1498","article-title":"S-Phase Arrest after Vincristine Treatment May Promote Hepatitis B Virus Replication","volume":"21","author":"Xu","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1038\/s41598-018-21847-3","article-title":"Cisplatin Enhances Hepatitis B Virus Replication and PGC-1\u03b1 Expression through Endoplasmic Reticulum Stress","volume":"8","author":"Li","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Moreno, A., and Garaigorta, U. (2017). Hepatitis B Virus and DNA Damage Response: Interactions and Consequences for the Infection. Viruses, 9.","DOI":"10.3390\/v9100304"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1158\/1541-7786.MCR-09-0112","article-title":"Promyelocytic Leukemia Nuclear Bodies Link the DNA Damage Repair Pathway with Hepatitis B Virus Replication: Implications for Hepatitis B Virus Exacerbation during Chemotherapy and Radiotherapy","volume":"7","author":"Chung","year":"2009","journal-title":"Mol. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.molcel.2017.05.015","article-title":"ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response","volume":"66","author":"Blackford","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/B978-0-12-380888-2.00003-0","article-title":"The ATM-Chk2 and ATR-Chk1 Pathways in DNA Damage Signaling and Cancer","volume":"108","author":"Smith","year":"2010","journal-title":"Adv. Cancer Res."},{"key":"ref_18","first-page":"4255","article-title":"ATM and ATR Signaling at a Glance","volume":"128","author":"Awasthi","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.mad.2008.02.014","article-title":"Modification of the ATM\/ATR Directed DNA Damage Response State with Aging and Long after Hepatocyte Senescence Induction in Vivo","volume":"129","author":"Panda","year":"2008","journal-title":"Mech. Ageing Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev-virology-092917-043534","article-title":"Virus DNA Replication and the Host DNA Damage Response","volume":"5","author":"Weitzman","year":"2018","journal-title":"Annu. Rev. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1099\/vir.0.044412-0","article-title":"DNA Viruses and the Cellular DNA-Damage Response","volume":"93","author":"Turnell","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.18821\/0507-4088-2018-63-4-165-170","article-title":"Increased Formation of Phosphorylated H2AX Foci in Nuclei of Cells Infected by Hepatitis B AND B+D Viruses","volume":"63","author":"Kostyushev","year":"2018","journal-title":"Vopr. Virusol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"597095","DOI":"10.1155\/2013\/597095","article-title":"DNA Damage Sensor \u03b3-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular Carcinoma","volume":"2013","author":"Matsuda","year":"2013","journal-title":"Sci. World J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1093\/nar\/gkv061","article-title":"Multiple Facets of Histone Variant H2AX: A DNA Double-Strand-Break Marker with Several Biological Functions","volume":"43","author":"Turinetto","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5059","DOI":"10.3748\/wjg.14.5059","article-title":"Cellular DNA Repair Cofactors Affecting Hepatitis B Virus Infection and Replication","volume":"14","author":"Zhao","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1099\/vir.0.000150","article-title":"Hepatitis B Virus X Protein Activates the ATM-Chk2 Pathway and Delays Cell Cycle Progression","volume":"96","author":"Kim","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"379","DOI":"10.4161\/cbt.23761","article-title":"Chemotherapy Induced DNA Damage Response: Convergence of Drugs and Pathways","volume":"14","author":"Woods","year":"2013","journal-title":"Cancer Biol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1677\/ERC-09-0020","article-title":"Hydrogen Peroxide Induces DNA Single- and Double-Strand Breaks in Thyroid Cells and Is Therefore a Potential Mutagen for This Organ","volume":"16","author":"Driessens","year":"2009","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/nbt.3199","article-title":"Epigenome Editing by a CRISPR-Cas9-Based Acetyltransferase Activates Genes from Promoters and Enhancers","volume":"33","author":"Hilton","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1134\/S0026893319010072","article-title":"Small Molecular Inhibitors of DNA Double Strand Break Repair Pathways Increase the ANTI-HBV Activity of CRISPR\/Cas9","volume":"53","author":"Kostyusheva","year":"2019","journal-title":"Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1038\/s41598-019-38526-6","article-title":"Suppressing the NHEJ Pathway by DNA-PKcs Inhibitor NU7026 Prevents Degradation of HBV CccDNA Cleaved by CRISPR\/Cas9","volume":"9","author":"Kostyushev","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1128\/jvi.66.7.4107-4116.1992","article-title":"The Arginine-Rich Domain of the Hepatitis B Virus Core Protein Is Required for Pregenome Encapsidation and Productive Viral Positive-Strand DNA Synthesis but Not for Virus Assembly","volume":"66","author":"Nassal","year":"1992","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"36483","DOI":"10.1038\/srep36483","article-title":"Minicircle HBV CccDNA with a Gaussia Luciferase Reporter for Investigating HBV CccDNA Biology and Developing CccDNA-Targeting Drugs","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-1-62703-484-5_13","article-title":"A Southern Blot Assay for Detection of Hepatitis B Virus Covalently Closed Circular DNA from Cell Cultures","volume":"Volume 1030","author":"Cai","year":"2013","journal-title":"Antiviral Methods and Protocols. Methods in Molecular Biology (Methods and Protocols)"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s12985-015-0447-5","article-title":"Mechanisms Downstream of Reverse Transcription Reduce Serum Levels of HBV DNA but Not of HBsAg in Chronic Hepatitis B Virus Infection","volume":"12","author":"Larsson","year":"2015","journal-title":"Virol. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1098\/rstb.2003.1368","article-title":"RAD51 Localization and Activation Following DNA Damage","volume":"359","author":"Tarsounas","year":"2004","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nrm3047","article-title":"The MRE11 Complex: Starting from the Ends","volume":"12","author":"Stracker","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s00795-009-0457-8","article-title":"Impact of Hepatitis B Virus X Protein on the DNA Damage Response during Hepatocarcinogenesis","volume":"42","author":"Matsuda","year":"2009","journal-title":"Med. Mol. Morphol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1440-1746.2010.06546.x","article-title":"Hepatitis B Virus x Protein in the Pathogenesis of Hepatitis B Virus-Induced Hepatocellular Carcinoma","volume":"26","author":"Kew","year":"2011","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.18632\/oncotarget.13904","article-title":"Oxidative Stress, a Trigger of Hepatitis C and B Virus-Induced Liver Carcinogenesis","volume":"8","author":"Ivanov","year":"2017","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1006\/bbrc.1997.6269","article-title":"Hepatitis B Virus X-Protein Binds Damaged DNA and Sensitizes Liver Cells to Ultraviolet Irradiation","volume":"232","author":"Capovilla","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/(SICI)1097-0215(19990315)80:6<875::AID-IJC13>3.0.CO;2-Z","article-title":"Hepatitis B Virus X Protein Inhibits Nucleotide Excision Repair","volume":"80","author":"Jia","year":"1999","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1128\/JVI.72.1.266-272.1998","article-title":"Hepatitis B Virus X Protein Interferes with Cellular DNA Repair","volume":"72","author":"Becker","year":"1998","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Schreiner, S., and Nassal, M. (2017). A Role for the Host DNA Damage Response in Hepatitis B Virus CccDNA Formation\u2014and Beyond?. Viruses, 9.","DOI":"10.3390\/v9050125"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"a012716","DOI":"10.1101\/cshperspect.a012716","article-title":"DNA Damage Sensing by the ATM and ATR Kinases","volume":"5","author":"Zou","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3389\/fonc.2018.00015","article-title":"DNA Damage, Repair, and Cancer Metabolism","volume":"8","author":"Turgeon","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.celrep.2018.03.076","article-title":"Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas","volume":"23","author":"Knijnenburg","year":"2018","journal-title":"Cell Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"43598","DOI":"10.1038\/srep43598","article-title":"Transcriptional and Post-Transcriptional Regulation of the Ionizing Radiation Response by ATM and P53","volume":"7","author":"Narayanan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_49","first-page":"rs3","article-title":"Parallel Profiling of the Transcriptome, Cistrome, and Epigenome in the Cellular Response to Ionizing Radiation","volume":"7","author":"Warnatz","year":"2014","journal-title":"Sci. Signal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1158\/1535-7163.MCT-12-1242","article-title":"Histone Deacetylase Regulation of ATM-Mediated DNA Damage Signaling","volume":"12","author":"Thurn","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.molcel.2016.02.001","article-title":"RNA Processing and Genome Stability: Cause and Consequence","volume":"61","author":"Wickramasinghe","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fmolb.2019.00061","article-title":"Beyond the Trinity of ATM, ATR, and DNA-PK: Multiple Kinases Shape the DNA Damage Response in Concert With RNA Metabolism","volume":"6","author":"Burger","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1038\/nn.3564","article-title":"EZH2-Mediated H3K27 Trimethylation Mediates Neurodegeneration in Ataxia-Telangiectasia","volume":"16","author":"Li","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5844","DOI":"10.1073\/pnas.0501916102","article-title":"DNA Repair Proteins Affect the Lifecycle of Herpes Simplex Virus 1","volume":"102","author":"Lilley","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1167\/iovs.13-13461","article-title":"Inhibition of Ataxia Telangiectasia Mutated (ATM) Kinase Suppresses Herpes Simplex Virus Type 1 (HSV-1) Keratitis","volume":"55","author":"Alekseev","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Moody, C.A., and Laimins, L.A. (2009). Human Papillomaviruses Activate the ATM DNA Damage Pathway for Viral Genome Amplification upon Differentiation. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000605"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00064-18","DOI":"10.1128\/mBio.00064-18","article-title":"Human Papillomaviruses Preferentially Recruit DNA Repair Factors to Viral Genomes for Rapid Repair and Amplification","volume":"9","author":"Mehta","year":"2018","journal-title":"MBio"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Jiang, M., Zhao, L., Gamez, M., and Imperiale, M.J. (2012). Roles of ATM and ATR-Mediated DNA Damage Responses during Lytic BK Polyomavirus Infection. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002898"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"13007","DOI":"10.1128\/JVI.79.20.13007-13017.2005","article-title":"Induction and Utilization of an ATM Signaling Pathway by Polyomavirus","volume":"79","author":"Dahl","year":"2005","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Anastasiou, O.E., Theissen, M., Verheyen, J., Bleekmann, B., Wedemeyer, H., Widera, M., and Ciesek, S. (2019). Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure. Viruses, 11.","DOI":"10.3390\/v11090863"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pisaturo, M., Macera, M., Alessio, L., Calo, F., and Coppola, N. (2019). Hepatitis B Virus (HBV) Reactivation Following Pharmacological Eradication of Hepatitis C Virus (HCV). Viruses, 11.","DOI":"10.3390\/v11090850"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Inoue, J., Nakamura, T., and Masamune, A. (2019). Roles of Hepatitis B Virus Mutations in the Viral Reactivation after Immunosuppression Therapies. Viruses, 11.","DOI":"10.3390\/v11050457"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"792","DOI":"10.7326\/M17-0377","article-title":"Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus: A Review of Cases Reported to the U.S. Food and Drug Administration Adverse Event Reporting System","volume":"166","author":"Cao","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.critrevonc.2015.10.017","article-title":"Hepatitis B and Cancer: A Practical Guide for the Oncologist","volume":"98","author":"Bozza","year":"2016","journal-title":"Crit. Rev. Oncol. 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