The level of c-fgr RNA is increased by EBNA-2, an Epstein-Barr virus gene required for B-cell immortalization.
The efficient immortalization of primary resting human B lymphocytes by Epstein-Barr virus (EBV) requires several viral genes and presumably the altered expression of an unknown number of cellular genes as well. In this paper, I show that infection of primary human B cells with EBV increased the transcript level of the proto-oncogene, c-fgr, 10-fold. This effect on the level of c-fgr transcripts in B cells was not secondary to blast formation, because levels of c-fgr RNA were also increased 10-fold in two proliferating EBV-negative Burkitt's lymphoma-derived cell lines, Ramos and BJAB, 2 days after infection with EBV. Two lines of evidence indicated that EBV nuclear antigen 2 (EBNA-2) mediates this increase in c-fgr RNA levels: acute infection of BJAB and Ramos cells by a mutant strain of EBV that lacked the EBNA-2 open reading frame, P3HR1, did not affect c-fgr RNA levels; and cell lines constitutively expressing only the EBNA-2 gene of EBV had increased levels of c-fgr RNA relative to those in the parental cell lines. Since P3HR1, a nonimmortalizing strain of EBV, failed to affect c-fgr RNA levels and since a viral gene required for B-cell immortalization was responsible for the induction of c-fgr, the data indicate a possible role of c-fgr expression in B-lymphocyte immortalization by EBV and a mechanism by which EBNA-2 contributes to the immortalizing activity of EBV.
Knutson
J C
JC
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison 53706.
D000956:Antigens, Viral / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D002051:Burkitt Lymphoma; D002460:Cell Line; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D019309:Epstein-Barr Virus Nuclear Antigens; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic; D019061:src-Family Kinases
D000956:Antigens, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012367:RNA, Viral; D011505:Protein-Tyrosine Kinases; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases