Hepatitis B virus (HBV) infection in mammals occurs by hijacking the epigenetic regulator such as Sp110, residing inside the promyelocytic leukemia- nuclear body (PML-NB) by the HBV encoded X protein (HBx) responsible for viral pathogenesis. The HBx induces oxidative stress to the host cells by forming reactive oxygen species (ROS) which leads to the activation of the host cell’s single strand DNA repair pathways such as Base excision repair. The oxidative damage due to HBx infection can be converted to double strand break during regeneration of hepatocytes leading to HBV induced hepatocellular carcinoma (HCC). Our earlier study has shown that HBx hijacks the host factor Sp110 to reprogram the epigenetic landscape of the chromatin for viral sustenance. Further, HBV infection can modulate histone modifications including H3K18Ac. The role of H3K18Ac during NHEJ is well established and it has been reported that SIRT7 deacetylates H3K18Ac to recruit 53BP1 for NHEJ. However, the molecular details of these epigenetic alterations have not been investigated in the backdrop of viral infection. Here we have employed a ROS scavenger for understanding the role of oxidative stress in double strand break repair during viral infection. Further, we establish a critical role of epigenetic regulator Sp110 in viral sustenance via modulating the ROS pathway. Thus, the present study intends to elucidate the role of ROS scavenger as a therapeutic strategy for HBV induced HCC, via epigenetically modulating the DNA damage response pathway.

Investigating the role of reactive oxygen species in progression of Hepatitis B virus (HBV) infection through epigenetic regulation of DNA damage response pathways

ACS Spring Meeting 2021

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