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Journal of Virology, March 2003, p. 3859-3865, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3859-3865.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Malignant Transformation of Epstein-Barr Virus-Negative Akata Cells by Introduction of the BARF1 Gene Carried by Epstein-Barr Virus

Wang Sheng,1 Gisèle Decaussin,1 Audrey Ligout,1 Kenzo Takada,2 and Tadamasa Ooka1*

Laboratoire de Virologie Moléculaire, UMR5537, CNRS, Faculté de Médecine R.T.H. Laennec, Université Claude Bernard Lyon-1, 69372 Lyon, France,1 Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan2

Received 23 July 2002/ Accepted 5 December 2002

Spontaneous loss of the Epstein-Barr virus (EBV) genome in the BL cell line Akata led to loss of tumorigenicity in SCID mice, suggesting an important oncogenic activity of EBV in B cells. We previously showed that introduction of the BARF1 gene into the human B-cell line Louckes induced a malignant transformation in newborn rats (M. X. Wei, J. C. Moulin, G. Decaussin, F. Berger, and T. Ooka, Cancer Res. 54:1843-1848, 1994). Since 1 to 2% of Akata cells expressed lytic antigens and expressed the BARF1 gene, we investigated whether introduction of the BARF1 gene into EBV-negative Akata cells can induce malignant transformation. Here we show that BARF1-transfected, EBV-negative Akata cells activated Bcl2 expression and induced tumor formation when they were injected into SCID mice. In addition, when EBV-positive Akata cells expressing a low level of BARF1 protein were injected into SCID mice, the expression of BARF1, as well as several lytic proteins, such as EA-D, ZEBRA, and a 135-kDa DNA binding protein, increased in tumor cells while no latent LMP1 and late gp220-320 expression was observed in tumor cells. These observations suggest that the BARF1 gene may be involved in the conferral of tumorigenicity by EBV.

* Corresponding author. Mailing address: Laboratoire de Virologie Moléculaire, IVMC, CNRS, Faculté de Médecine R. Laennec, Rue G. Paradin, 69372 Lyon, Cedex 08, France. Phone: (33) 04-78-01-18-36. Fax: (33) 04-78-74-96-68. E-mail: ooka{at}laennec.univ-lyon1.fr.

Journal of Virology, March 2003, p. 3859-3865, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3859-3865.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Seto, E., Ooka, T., Middeldorp, J., Takada, K. (2008). Reconstitution of Nasopharyngeal Carcinoma-Type EBV Infection Induces Tumorigenicity. Cancer Res. 68: 1030-1036 [Abstract] [Full Text]  


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