Interferon signaling during Hepatitis B Virus (HBV) infection and HBV-associated hepatocellular carcinoma

Chronic Hepatitis B Virus (HBV) infection is linked to hepatocellular carcinoma (HCC) pathogenesis. The World Health Organization estimates that globally 257 million people are chronic HBV carriers at risk of developing liver cancer. Current therapies for prevention and treatment of HCC are inadequate. Although interferon-based treatment strategies hold great promise for combating chronic infection and HCC, many patients do not respond to the IFN-based drugs for reasons not completely understood. Interferon signaling plays key roles in activation of innate and adaptive immunity. However, HBV has evolved various mechanisms to suppress IFN signaling. In this review, we present the basics about HBV infection and interferon signaling. Next, we discuss mechanisms through which HBV downregulates the function -activity and transcription- of the transcription factor STAT1 during acute and chronic infection. STAT1 is activated in response to all types (I/II/III) of interferon signaling and is essential in mediating all types (I/II/III) of interferon responses. Lastly, we discuss emerging evidence from different human cancers linking loss of interferon signaling to aggressive cancer and cancer stem cells. Whether the same occurs during HBV-associated hepatocarcinogenesis is discussed and currently under investigation.