Open Access
Viruses, volume 11, issue 11, pages 997
ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage
Kostyusheva Anastasiya
1
,
Brezgin Sergey
1, 2
,
Bayurova Ekaterina
3, 4
,
Gordeychuk Ilya
3, 4, 5
,
Isaguliants Maria
3, 4, 6, 7
,
Goptar Irina
8
,
Урусов Ф. А.
8
,
Nikiforova Anastasiya
8
,
Volchkova Elena
5
,
Chulanov Vladimir
1, 5, 9
1
National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, Moscow 127994, Russia
|
6
Department of Pathology, Riga Stradins University, LV-1007 Riga, Latvia
|
Publication type: Journal Article
Publication date: 2019-10-31
PubMed ID:
31683589
Infectious Diseases
Virology
Abstract
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.
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Citations by publishers
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Kostyusheva A. et al. ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage // Viruses. 2019. Vol. 11. No. 11. p. 997.
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Kostyusheva A., Brezgin S., Bayurova E., Gordeychuk I., Isaguliants M., Goptar I., Урусов Ф. А., Nikiforova A., Volchkova E., Kostyushev D., Chulanov V. ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage // Viruses. 2019. Vol. 11. No. 11. p. 997.
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TY - JOUR
DO - 10.3390/v11110997
UR - https://doi.org/10.3390%2Fv11110997
TI - ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage
T2 - Viruses
AU - Kostyusheva, Anastasiya
AU - Goptar, Irina
AU - Nikiforova, Anastasiya
AU - Kostyushev, Dmitry
AU - Brezgin, Sergey
AU - Isaguliants, Maria
AU - Volchkova, Elena
AU - Bayurova, Ekaterina
AU - Gordeychuk, Ilya
AU - Урусов, Ф. А.
AU - Chulanov, Vladimir
PY - 2019
DA - 2019/10/31 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 997
IS - 11
VL - 11
PMID - 31683589
SN - 1999-4915
ER -
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@article{2019_Kostyusheva,
author = {Anastasiya Kostyusheva and Irina Goptar and Anastasiya Nikiforova and Dmitry Kostyushev and Sergey Brezgin and Maria Isaguliants and Elena Volchkova and Ekaterina Bayurova and Ilya Gordeychuk and Ф. А. Урусов and Vladimir Chulanov},
title = {ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage},
journal = {Viruses},
year = {2019},
volume = {11},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {oct},
url = {https://doi.org/10.3390%2Fv11110997},
number = {11},
pages = {997},
doi = {10.3390/v11110997}
}
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Kostyusheva, Anastasiya, et al. “ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage.” Viruses, vol. 11, no. 11, Oct. 2019, p. 997. https://doi.org/10.3390%2Fv11110997.