Yan Yang, Anding Liu, Shenpei Liu, Chunyan Zhang, Xiang Liu, Hongping Huang, Jingjiao Song, Yan Chen, Yuan Yu and Xuefeng Zhou
Liver is one of the target organs for double-stranded DNA (dsDNA)-vector mediated gene delivery due to the highly efficient uptake of gene therapy vectors. Recently dsDNA was described as a pathogen associated molecular pattern that could be recognized by intracellular DNA sensors. Herein, we explored the possibility that dsDNA may change the intracellular innate immune responses of hepatocyte-derived cell and therefore regulate the replication of hepatitis B virus (HBV). A hepatoma cell line HepG2.2.15 which derived from HepG2 with integrated HBV genome, were treated with poly (dA-dT), a synthetic double-stranded DNA molecule. Unexpectedly, HBV replication was up-regulated after poly (dA-dT) transfection in HepG2.2.15 despite the delayed activation of ISGs. There was no nuclear-plasma translocation of IRF3 or NF-κB observed at a early stage. Treatment of HepG2.2.15 cells with supernatant harvested from the cells transfected with poly (dA-dT) indicating that poly (dA-dT) -enhanced HBV replication was predominantly mediated by not secreted cytokines, but intracellular factors. By blocking the cellular signal pathways with inhibitors, we found that U0126, an inhibitor of ERK1/2, could abolish the poly (dA-dT) enhanced HBV replication. Pathway-scan results also indicated that phosphorylated MEK1/2 was enhanced after poly (dA-dT) transfection. Whether this HBV replicating enhancement is good for HBV infection disease outcome needs to be further investigated.
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