Hepatitis B virus causes DNA double-strand breaks via XRCC3 down-regulation and ROS stress

B20

The hepatitis B virus (HBV) causes DNA damage such as nucleotide excision as well as various types of liver diseases. Furthermore, DNA double-strand break (DSB) is a very hazardous DNA damage that can cause carcinogenesis or apoptosis. However, the correlation between HBV and DNA DSB has been unclear thus far. We first analyzed the γH2AX foci intensity, which is known as a marker of DNA DSB formation, at the cell lines where HBV or HBx was stably expressed , and found out that DNA DSBs increased. In addition, treatment with the antioxidant, N-acetylcysteine (NAC) depleted the reactive oxygen species (ROS) level, which reduced the DNA DSBs. To find the other cause of the increase in DNA DSBs due to HBV, we analyzed the alteration of the DNA DSB repair genes expressions in HBV or HBx stable cell lines. As a result, only XRCC3 was reduced by HBV. Moreover, based on the findings that DNA DSBs increased during XRCC3 shRNA expression, we concluded that XRCC3 was an essential repair gene for repairing DNA DSBs. The level of XRCC3 expression was different for the human liver tissues depends on the presence of HBV; XRCC3 expression decreased according to the HBV titer. In conclusion, our findings suggest that HBV increases DNA DSBs according to the down-regulation of XRCC3 expression and the raising of ROS stress.