The C-terminal region of the hepatitis B virus X protein is essential for its stability and function.
More than 350 million people worldwide are chronically infected with the human hepatitis B virus (HBV). Chronic HBV infections are associated with the development of hepatocellular carcinoma. While the mechanism of HBV-associated carcinoma remains undefined, it is thought to involve a combination of a continuous inflammatory response to HBV-infected hepatocytes and activities of HBV proteins such as the HBV X protein (HBx). HBx stimulates HBV replication; however, the mechanism by which HBx stimulates HBV replication remains incompletely understood. Studies performed with the woodchuck hepatitis virus (WHV) in woodchucks demonstrated that a C-terminally truncated mutant of the WHV X protein could not stimulate WHV replication. However, whether the C-terminus of HBx is important for HBx-stimulation of HBV replication is unclear. We have constructed C-terminal truncation mutants of HBx and have demonstrated that the C-terminus of HBx impacts HBx stability, HBx activation of transcription, and HBx stimulation of HBV replication. These observations highlight the impact of the HBx C-terminus on HBx activities and the importance of directly analyzing HBx expression and functions in HBV-associated tumors that contain chromosomal integrants of HBV with truncations of the HBx gene.
Lizzano
Rebecca A
RA
Graduate Program in Molecular and Cellular Biology and Genetics, Drexel University College of Medicine, Philadelphia, PA 19102, United States.
Yang
Bei
B
Clippinger
Amy J
AJ
Bouchard
Michael J
MJ
D002460:Cell Line; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D055550:Protein Stability; D017384:Sequence Deletion; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication
D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein