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Comparative study of the different activities of hepatitis B virus whole-X protein and HBx in hepatocarcinogenesis by proteomics and bioinformatics analysis

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Abstract

The hepatitis B virus (HBV) whole-X gene comprises the HBV X gene and the 168-bp region immediately upstream. Although the functions of HBx in hepatocarcinogenesis are well known, the activity of the HBV whole-X protein (HBwx), with 56 additional amino acids, has not yet been explored. In this study, proteomic and bioinformatic analysis was done to determine the protein interaction profiles of HBwx and HBx and to describe their functions in carcinogenesis. A total of 203 proteins were identified that interacted with HBwx, of which 149 were unique, the rest interacting also with HBx, and 73 % (148/203) of these proteins are involved in carcinogenesis. Gene ontology (GO) analysis showed that HBwx- and HBx-interacting proteins are involved in different processes, the former mainly in biosynthetic processes (glycolysis, cell-cycle functions, and protein folding), and the latter mainly in localization, viral transcription, biological adhesion and angiogenesis. Pathway networks analysis revealed that proteins interacting with HBx participate mainly in oxidative phosphorylation, localization, the cytoskeleton, and cell adhesion. In contrast, more-specific functional analysis showed that proteins interacting with HBwx are involved in apoptosis and survival, cell-cycle functions, glycolysis, and gluconeogenesis (Pathway Maps); to cellular macromolecular complex assembly, protein folding and mRNA metabolic process (GO Processes); and to regulation of protein folding in the endoplasmic reticulum and cytoplasm, transcription, cell cycle G2-M and cytoskeleton rearrangement (Process Networks). In conclusion, this study shows that HBwx functions in carcinogenesis in a way that is different from that of HBx.

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Acknowledgments

This work was supported by the Natural Scientific Foundation of China (No. 31100129).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi Province, China

    Yu Zhang, Jinfeng Liu, Yingli He, Ruitian Yi, Yinghua Niu, Tianyan Chen & Yingren Zhao

  2. Shaanxi Provincial Infectious Diseases Hospital and Xi’an Eighth Hospital Affiliated to Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi Province, China

    Hongli Liu

  3. Neurosurgery Laboratory of The Fourth Military Medical University, Xi’an, 710032, Shaanxi Province, China

    Qian Yang

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  1. Yu Zhang
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  2. Jinfeng Liu
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  3. Hongli Liu
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  5. Ruitian Yi
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Correspondence to Yingren Zhao.

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Zhang, Y., Liu, J., Liu, H. et al. Comparative study of the different activities of hepatitis B virus whole-X protein and HBx in hepatocarcinogenesis by proteomics and bioinformatics analysis. Arch Virol 160, 1645–1656 (2015). https://doi.org/10.1007/s00705-015-2421-3

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  • DOI: https://doi.org/10.1007/s00705-015-2421-3

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