Malignant transformation of Epstein-Barr virus-negative Akata cells by introduction of the BARF1 gene carried by Epstein-Barr virus.
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.
Sheng
Wang
W
Laboratoire de Virologie Moléculaire, UMR5537, CNRS, Faculté de Médecine R.T.H. Laennec, Université Claude Bernard Lyon-1, 69372 Lyon, France.
Decaussin
Gisèle
G
Ligout
Audrey
A
Takada
Kenzo
K
Ooka
Tadamasa
T
D000818:Animals; D002051:Burkitt Lymphoma / Q000821:virology*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
C086495:BARF1 protein, Human herpesvirus 4; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins