New discoveries hold promise for treatment of Hepatitis B virus infection

A University of Colorado at Boulder-led team has discovered two prime targets of the Hepatitis B virus in liver cells, findings that could lead to treatment of liver disease in some of the 400 million people worldwide currently infected with the virus.

CU-Boulder Professor Ding Xue, who led the studies, said scientists have been looking for cellular targets of the Hepatitis B virus, or HBV, for more than three decades.

Infections from HBV promote hepatitis (inflammation of the liver), cirrhosis (scarring of the liver) and liver cancer and can be transmitted through blood and bodily fluids, unprotected sex, unsterile needles and from infected mother to offspring during birth.

Xue said scientists have known for some time that HBV encodes a pathogenic, tumour-promoting protein known as HBx, but how it works has remained largely unknown.

In two new studies, Xue and his colleagues showed that the ''host targets'' of HBx in human cells are two small cell proteins known as Bcl-2 and Bcl-xL, both of which are well-known cell death inhibitors but which have not previously been implicated in HBV infection.

HBx uses a particular ''motif,'' a small string of protein building blocks known as amino acids that resemble those seen in some cell death-causing proteins, to interact with the Bcl-2 and Bcl-xL targets and stimulate an elevation of calcium in the host cell. The calcium elevation then triggers both viral HBV replication and cell death, said Xue.