Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis B virus by inducing cGAS-dependent innate immune response

Hepatitis B virus (HBV) causes hepatic diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. These diseases are closely associated with persistent HBV infection. To prevent the progression of hepatic diseases, it is thus important to suppress persistent HBV infection. Da...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2018-10, Vol.504 (4), p.672-678
Main Authors: Imai, Hirotaka, Dansako, Hiromichi, Ueda, Youki, Satoh, Shinya, Kato, Nobuyuki
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Cell Line
CELL PROLIFERATION
Cell Proliferation - drug effects
Cyclic GMP-AMP synthetase
Daunorubicin
Daunorubicin - pharmacology
DNA damage response
DNA DAMAGES
EBOLA VIRUSES
Gene Expression - drug effects
Hep G2 Cells
HEPATITIS
Hepatitis B virus
Hepatitis B virus - drug effects
Hepatitis B virus - physiology
Hepatocytes - immunology
Hepatocytes - metabolism
Hepatocytes - virology
HEPATOMAS
Humans
Immunity, Innate - drug effects
Innate immune response
INTERFERON
LIVER CELLS
LIVER CIRRHOSIS
Nucleotidyltransferases - genetics
Nucleotidyltransferases - metabolism
Topoisomerase II Inhibitors - pharmacology
Topoisomerase II poison
Virus Replication - drug effects
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Summary:Hepatitis B virus (HBV) causes hepatic diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. These diseases are closely associated with persistent HBV infection. To prevent the progression of hepatic diseases, it is thus important to suppress persistent HBV infection. Daunorubicin (DNR), a topoisomerase II (Top II) poison, is a clinically used anticancer agent with a wide spectrum of activity against malignancies. DNR was recently reported to cause DNA damage-dependent interferon (IFN)-β induction through exogenous cyclic GMP-AMP synthetase (cGAS) and subsequently to suppress Ebola virus replication. In the present study, we demonstrated that DNR caused the inhibition of cell proliferation, but not cell death, through the DNA damage response in immortalized human hepatocyte NKNT-3/NTCP cells. Interestingly, DNR triggered the endogenous cGAS-dependent innate immune response and subsequently suppressed viral production of HBV in NKNT-3/NTCP cells. Top II poisons may be anti-HBV drug candidates.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.08.195