Using proteomics to identify the HBx interactome in hepatitis B virus: how can this inform the clinic?

Abstract

Hepatitis B virus (HBV) is a small and enveloped DNA virus, of which chronic infection is the main risk factor of liver cirrhosis and hepatocellular carcinoma. Hepatitis B virus X protein (HBx) is a multifunctional protein encoded by HBV genome, which have significant effects on HBV replication and pathogenesis. Through directly interacting with cellular proteins, HBx is capable to promote HBV replication, regulate transcription of host genes, disrupt protein degradation, modulate signaling pathway, manipulate cell death and deregulate cell cycle. In this review, we briefly discuss the diversified effects of HBx-interactome and their potential clinical significances.

Keywords::

• clinical significance
• hepatitis B virus
• hepatitis B virus X protein interactome
• hepatocellular carcinoma
• proteomics

Financial & competing interests disclosure

This work was supported by grants from the National 973 Basic Research rogram of China (2013CB911300, 2012CB518900), the National Science and Technology Major Project (2012ZX09501001-003), and the atural Science Foundation of China(81225015, 81072022 and 81172173). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Hepatitis B virus X protein-interacting proteins are identified with various experimental measures including yeast two-hybrid screening and affinity purification followed by mass spectrometry.

• Hepatitis B virus X protein interacts with a diversity of cellular proteins to promote hepatitis B virus replication, regulate transcription of host genes, disrupt protein degradation, modulate signaling pathway, manipulate cell death and deregulate cell cycle.

Notes

GST: Glutathione-S-transferase; HBx: Hepatitis B virus X protein; MS: Mass spectrometry; PTM: Posttranslational modification; PPI: Protein–protein interaction; TAP: Tandem affinity purification.