Archives of Virology

, Volume 161, Issue 5, pp 1347–1352 | Cite as

The unique role of the hepatitis virus B X protein on HEK 293 cell morphology and cellular change

  • Yongjie Zhang
  • Jiali Cheng
  • Chaohong LiuEmail author
Brief Report


The function of the hepatitis B virus X protein (HBx) has been investigated in hepatoma cell lines before; however, its function in the canonical HEK 293 cell line has not been addressed. In this study, we found that HBx increased cellular interaction by fusing the gap between HEK 293 cells, which is different from what has been reported previously. We also found that HBx enhanced the expression of E-cadherin in hepatoma cell lines instead of decreasing it as reported previously. The increase in E-cadherin was mediated by the enhanced levels of Src, which also differs from previous reports. Finally, we observed that HBx can accelerate cell growth by increasing the percentage of cells that are positioned at the division stage. Further analysis showed that the increased growth was caused by increased CDK4 expression and Ki67+ populations. Additionally, reduced apoptosis was found in HEK 293 cells expressing HBx due to an increase in the anti-apoptotic protein-Bcl2. Collectively, the different functions of HBx in HEK 293 cells suggest that its role is cell dependent.


HepG2 Cell CDK4 Expression Chang Liver Cell Western Blot Profile Centrosome Dynamic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Drs. Vera Stupina and Megan Young for critically reading the manuscript. This work was supported by a project from Chongqing Science and Technology Commission (cstc2015shmszx0196). The authors have no conflicts of interest to declare. This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Ahn JY, Jung EY, Kwun HJ, Lee CW, Sung YC, Jang KL (2002) Dual effects of hepatitis B virus X protein on the regulation of cell-cycle control depending on the status of cellular p53. J Gen Virol 83:2765–2772CrossRefPubMedGoogle Scholar
  2. 2.
    Arzumanyan A, Friedman T, Kotei E, Ng IO, Lian Z, Feitelson MA (2012) Epigenetic repression of E-cadherin expression by hepatitis B virus × antigen in liver cancer. Oncogene 31:563–572PubMedPubMedCentralGoogle Scholar
  3. 3.
    Beck J, Nassal M (2007) Hepatitis B virus replication. WJG 13:48–64CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP (1989) Hepatitis B virus and hepatocellular carcinoma–treatment of HBV carriers with Phyllanthus amarus. Cancer Detect Prev 14:195–201PubMedGoogle Scholar
  5. 5.
    Byeon IJ, Li H, Song H, Gronenborn AM, Tsai MD (2005) Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67. Nat Struct Mol Biol 12:987–993CrossRefPubMedGoogle Scholar
  6. 6.
    Fung SK, Lok AS (2004) Viral hepatitis in 2003. Curr Opin Gastroenterol 20:241–247CrossRefPubMedGoogle Scholar
  7. 7.
    Hirohashi S (1998) Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153:333–339CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hirohashi S, Kanai Y (2003) Cell adhesion system and human cancer morphogenesis. Cancer Sci 94:575–581CrossRefPubMedGoogle Scholar
  9. 9.
    Kay A, Zoulim F (2007) Hepatitis B virus genetic variability and evolution. Virus Res 127:164–176CrossRefPubMedGoogle Scholar
  10. 10.
    Klein NP, Schneider RJ (1997) Activation of Src family kinases by hepatitis B virus HBx protein and coupled signaling to Ras. Mol Cell Biol 17:6427–6436CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Lara-Pezzi E, Roche S, Andrisani OM, Sanchez-Madrid F, Lopez-Cabrera M (2001) The hepatitis B virus HBx protein induces adherens junction disruption in a src-dependent manner. Oncogene 20:3323–3331CrossRefPubMedGoogle Scholar
  12. 12.
    Lee JO, Kwun HJ, Jung JK, Choi KH, Min DS, Jang KL (2005) Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1. Oncogene 24:6617–6625CrossRefPubMedGoogle Scholar
  13. 13.
    Li T, Robert EI, van Breugel PC, Strubin M, Zheng N (2010) A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery. Nat Struct Mol Biol 17:105–111CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Li W, Miao X, Qi Z, Zeng W, Liang J, Liang Z (2010) Hepatitis B virus X protein upregulates HSP90alpha expression via activation of c-Myc in human hepatocarcinoma cell line, HepG2. Virol J 7:45CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Liu C, Miller H, Hui KL, Grooman B, Bolland S, Upadhyaya A, Song W (2011) A balance of Bruton’s tyrosine kinase and SHIP activation regulates B cell receptor cluster formation by controlling actin remodeling. J Immunol 187:230–239CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Liu C, Bai X, Wu J, Sharma S, Upadhyaya A, Dahlberg CI, Westerberg LS, Snapper SB, Zhao X, Song W (2013) N-wasp is essential for the negative regulation of B cell receptor signaling. PLoS Biol 11:e1001704CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Liu C, Wang Y, Wu C, Pei R, Song J, Chen S, Chen X (2013) Dioscin’s antiviral effect in vitro. Virus Res 172:9–14CrossRefPubMedGoogle Scholar
  18. 18.
    Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, van Schie RC, LaFace DM, Green DR (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med 182:1545–1556CrossRefPubMedGoogle Scholar
  19. 19.
    Poligone B, Gilmore ES, Alexander CV, Oleksyn D, Gillespie K, Zhao J, Ibrahim SF, Pentland AP, Brown MD, Chen L (2015) PKK suppresses tumor growth and is decreased in squamous cell carcinoma of the skin. J Invest Dermatol 135:869–876CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Schmid I, Krall WJ, Uittenbogaart CH, Braun J, Giorgi JV (1992) Dead cell discrimination with 7-amino-actinomycin D in combination with dual color immunofluorescence in single laser flow cytometry. Cytometry 13:204–208CrossRefPubMedGoogle Scholar
  21. 21.
    Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR, Harris CC (1994) Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc Natl Acad Sci USA 91:2230–2234CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wen Y, Golubkov VS, Strongin AY, Jiang W, Reed JC (2008) Interaction of hepatitis B viral oncoprotein with cellular target HBXIP dysregulates centrosome dynamics and mitotic spindle formation. J Biol Chem 283:2793–2803CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  1. 1.Chongqing City Key Lab of Child Infection and ImmunityChildren’s Hospital of Chongqing Medical UniversityChongqingChina
  2. 2.Department of Pathogen Biology, School of Basic MedicineHuazhong University of Science and TechnologyWuhanChina

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