Hepatitis B virus (HBV) has come a long way from first being linked to "Australian Antigen" to now being one of the most dreadful viruses known to humans; chronically infecting 250 million people worldwide, HBV resulted in 887,000 deaths just in 2015 alone. Chronic HBV infection is a leading cause for hepatocellular carcinoma (HCC), which in turn is the second most prevalent cause of death related to cancer worldwide.
Mechanistically, the advancement from HBV infection to HCC is not fully understood. However, recent studies may indicate that alterations by HBV to the cellular metabolism could be one of the factors that lead to hepatocyte transformation. In our lab, we are trying to address this question by focusing on glucose metabolism using primary rat hepatocytes (PRHs) and recombinant adenovirus infection model system. We show that AdHBV infected PRHs have an increased glucose uptake rate as compared to the controls. We also see an effect of varying glucose concentration on HBcAg (HBV core protein) levels and on HBV replication, suggesting a major role of glucose utilization on viral pathogenesis.
Furthermore, to understand how glucose is being utilized by the hepatocytes to favor HBV, we would like to propose that upregulation of glucose uptake could be mediated by PKM2 (pyruvate kinase M2)/HIF1a (hypoxia inducible factor 1a) axis, which is one of the most commonly activated pathways in cancers, wherein glucose is then subsequently shunted towards anabolic PPP (pentose phosphate pathway) generating excess nucleic acids required for viral replication.
Understanding how HBV manipulates cellular activities that subsequently cause HCC may reveal some new potential therapeutic targets.