TY - JOUR
T1 - Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis B virus by inducing cGAS-dependent innate immune response
AU - Imai, Hirotaka
AU - Dansako, Hiromichi
AU - Ueda, Youki
AU - Satoh, Shinya
AU - Kato, Nobuyuki
N1 - Funding Information:
We thank Marie Iwado and Masayo Takemoto for their technical assistance. This research was supported by the Japan Agency for Medical Research and Development (AMED) under grant numbers JP18fk0310107 and JP18fk0310103 .
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/10/12
Y1 - 2018/10/12
N2 - 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.
AB - 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.
KW - Cyclic GMP-AMP synthetase
KW - DNA damage response
KW - Daunorubicin
KW - Hepatitis B virus
KW - Innate immune response
KW - Topoisomerase II poison
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U2 - 10.1016/j.bbrc.2018.08.195
DO - 10.1016/j.bbrc.2018.08.195
M3 - Article
C2 - 30209005
AN - SCOPUS:85053007249
VL - 504
SP - 672
EP - 678
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -
