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

Imai, Hirotaka, Dansako, Hiromichi, Ueda, Youki, Satoh, Shinya, Kato, Nobuyuki
Biochemical and biophysical research communications 2018 v.504 no.4 pp. 672-678
DNA, DNA damage, DNA topoisomerase (ATP-hydrolysing), Ebolavirus, Hepatitis B virus, cell death, cell proliferation, chronic hepatitis, daunorubicin, hepatoma, humans, innate immunity, interferons, liver cirrhosis, virus replication
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.