ATM and atr expression potentiates hbv replication and contributes to reactivation of hbv infection upon DNA damage

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dc.contributor.authorKostyusheva, Anastasiya
dc.contributor.authorBrezgin, Sergey
dc.contributor.authorBayurova, Ekaterina
dc.contributor.authorGordeychuk, Ilya
dc.contributor.authorIsaguliants, Maria
dc.contributor.authorGoptar, Irina
dc.contributor.authorUrusov, Felix
dc.contributor.authorNikiforova, Anastasiya
dc.contributor.authorVolchkova, Elena
dc.contributor.authorKostyushev, Dmitry
dc.contributor.authorChulanov, Vladimir
dc.contributor.institutionDepartment of Pathology
dc.date.accessioned2021-06-15T09:15:01Z
dc.date.available2021-06-15T09:15:01Z
dc.date.issued2019-10-31
dc.descriptionFunding Information: Funding: This work was performed within RSF grant no. 16-15-10426. Funding Information: National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, Moscow 127994, Russia; Seegez@mail.ru (S.B.); vladimir.chulanov@rcvh.ru (V.C.) Institute of Immunology, Federal Medical Biological Agency, Moscow 115522, Russia NF Gamaleya Research Center of Epidemiology and Microbiology, Moscow 123098, Russia; p1ngv1n2009@yandex.ru (E.B.); lab.gord@gmail.com (I.G.); maria.issagouliantis@rsu.lv (M.I.) Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow 108819, Russia Sechenov First Moscow State Medical University, Moscow 119146, Russia; az@rcvh.ru Department of Pathology, Riga Stradins University, LV-1007 Riga, Latvia Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 76 Stockholm, Sweden Izmerov Research Institute of Occupational Health, Gene Engineering and Biotechnology, Moscow 105275, Russia; probirka@list.ru (I.G.); flanger.fx@mail.ru (F.U.); utkina.anastasia@gmail.com (A.N.) Central Research Institute of Epidemiology, Moscow 111123, Russia Correspondence: kostyusheva_ap@mail.ru (A.K.); dkostushev@gmail.com (D.K.) Publisher Copyright: © 2019 by the authors.
dc.description.abstractChronic 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.en
dc.description.statusPeer reviewed
dc.format.extent2972827
dc.identifier.citationKostyusheva, A, Brezgin, S, Bayurova, E, Gordeychuk, I, Isaguliants, M, Goptar, I, Urusov, F, Nikiforova, A, Volchkova, E, Kostyushev, D & Chulanov, V 2019, 'ATM and atr expression potentiates hbv replication and contributes to reactivation of hbv infection upon DNA damage', Viruses, vol. 11, no. 11, 997. https://doi.org/10.3390/v11111000
dc.identifier.doi10.3390/v11111000
dc.identifier.issn1999-4915
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/5028
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85074547297&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofViruses
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAtm
dc.subjectAtr
dc.subjectCrispr/Cas9
dc.subjectCrispra
dc.subjectDcas9
dc.subjectDNA damage
dc.subjectHBV reactivation
dc.subjectPhosphorylated H2AX
dc.subjectReplication
dc.subjectShrna
dc.subjectYh2Ax
dc.subject3.3 Health sciences
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectInfectious Diseases
dc.subjectVirology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleATM and atr expression potentiates hbv replication and contributes to reactivation of hbv infection upon DNA damageen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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