Hepatitis B virus (HBV) is a human hepatotropic pathogen causing hepatocellular carcinoma. We recently obtained HBV-susceptible immortalized human hepatocyte NKNT-3 by exogenously expressing NTCP and its derived cell clones, #28.3.8 and #126.96.36.199 exhibiting different levels of HBV susceptibility. In the present study, we showed that HBV infection activated the ATM-Chk2 signaling pathway in #188.8.131.52 cells but not in #28.3.8 cells. Both the cell culture supernatant and extracellular vesicles (EVs) derived from HBV-infected #184.108.40.206 cells also activated the ATM-Chk2 signaling pathway in naïve #220.127.116.11 cells. Interestingly, EVs derived from HBV-infected #18.104.22.168 cells included higher level of mitochondrial DNA (mtDNA) than those from HBV-infected #28.3.8 cells. Based on our results, we propose the novel model that EVs mediate the activation of ATM-Chk2 signaling pathway by the intercellular transfer of mtDNA in HBV-infected human hepatocyte.
|Journal||FASEB journal : official publication of the Federation of American Societies for Experimental Biology|
|Publication status||Published - Jun 2021|