Occult hepatitis B virus infection with low viremia induces DNA damage, apoptosis and oxidative stress in peripheral blood lymphocytes

Abstract

Occult HBV infections (OHBI) are often associated with poor therapeutic response and increased risk of developing hepatocellular carcinoma. Despite a decade of research, OHBI still remains an intricate issue and much is yet to be defined about their possible immune implications. As HBV is known to infect peripheral blood lymphocytes, the present study aimed to explore the molecular mechanisms underlying DNA damage response triggered due to OHBI in host cells. The study was divided into three groups i.e. group A (OHBI patients n = 30, viral load ≤100 IU/mL); group B (chronic HBV patients, n = 30) and group C (controls, n = 30). Peripheral blood lymphocytes were isolated and DNA damage response, apoptosis and oxidative stress were the studied parameters. A significant increase in the phosphorylation of DNA damage response proteins (ATM, ATR, H2AX and p53) in OHBI in comparison to controls suggested that OHBI induces DNA damage in peripheral blood lymphocytes and elicit a PI3 kinase mediated cellular response. In addition, increased DNA fragmentation, circulating nucleosome levels and mitochondrial membrane depolarization observed in OHBI group indicated that this damage might lead to cellular demise and immune hypo-responsiveness. Moreover, OHBI was also observed to be strongly associated with oxidative stress as suggested by the augmented levels of DCF fluorescence and depleted GR activity. Collectively, these results provide the basic knowledge about the genotoxic effects of OHBI in peripheral blood lymphocytes. Such studies may possibly open up new avenues for identifying novel therapeutic targets for viral hepatitis.