ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage
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.
Citations by journals
1
2
3
|
|
International Journal of Molecular Sciences
|
International Journal of Molecular Sciences
3 publications, 17.65%
|
Microorganisms
|
Microorganisms
1 publication, 5.88%
|
Molecular Biology
|
Molecular Biology
1 publication, 5.88%
|
Future Virology
|
Future Virology
1 publication, 5.88%
|
Viruses
|
Viruses
1 publication, 5.88%
|
Infectious Agents and Cancer
|
Infectious Agents and Cancer
1 publication, 5.88%
|
Clinics in Liver Disease
|
Clinics in Liver Disease
1 publication, 5.88%
|
Biochemical and Biophysical Research Communications
|
Biochemical and Biophysical Research Communications
1 publication, 5.88%
|
Molecular Therapy - Nucleic Acids
|
Molecular Therapy - Nucleic Acids
1 publication, 5.88%
|
Aquaculture
|
Aquaculture
1 publication, 5.88%
|
World Journal of Gastroenterology
|
World Journal of Gastroenterology
1 publication, 5.88%
|
Free Radical Biology and Medicine
|
Free Radical Biology and Medicine
1 publication, 5.88%
|
Computers in Biology and Medicine
|
Computers in Biology and Medicine
1 publication, 5.88%
|
1
2
3
|
Citations by publishers
1
2
3
4
5
6
|
|
Elsevier
|
Elsevier
6 publications, 35.29%
|
Multidisciplinary Digital Publishing Institute (MDPI)
|
Multidisciplinary Digital Publishing Institute (MDPI)
5 publications, 29.41%
|
Pleiades Publishing
|
Pleiades Publishing
1 publication, 5.88%
|
Future Medicine
|
Future Medicine
1 publication, 5.88%
|
Springer Nature
|
Springer Nature
1 publication, 5.88%
|
Baishideng Publishing Group
|
Baishideng Publishing Group
1 publication, 5.88%
|
Cold Spring Harbor Laboratory
|
Cold Spring Harbor Laboratory
1 publication, 5.88%
|
1
2
3
4
5
6
|
- 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.