Functional analysis of pro-apoptotic activity of hepatitis B virus (HBV) : role of BcL2 homology domain 3 (BH3) in HBV DNA polymerase and HBX

Hepatitis B virus (HBV) infection leads to a wide range of liver disease, including viral hepatitis and hepatocellular carcinoma (HCC). Viral hepatitis is characterized by an inflammatory reaction in the infected liver cells, and is associated with cell damage and death. One of the typical processes of cell death is apoptosis which is generally considered to be a mechanism of host defense against viral infections. Apoptosis is a highly conserved, tightly controlled self-destruction process to ablate damaged and neoplastic cells in multicellular organisms. On the other hand, virus have evolved strategies to counteract and regulate apoptosis in order to maximize the production of virus progeny and promote the spread of virus progeny to neighbouring cells. Despite its widely accepted non-cytolytic nature, HBV proteins have been linked to apoptosis. However, little is known about the conditions under which HBV included apoptosis of host hepatocytes following natural infection and whether or how it may counteract apoptosis. Using a cell based system, HBV replication trigged by transfection of replicative viral genome was found to include apoptosis in cultured cells. Further, the BH3-containing spilces variant (HBSP) which was previously reported to include apoptosis in HepG2 cells was expressed during HBV replication.RG 53/0