[Studies on transforming functions of Epstein-Barr virus-specific proteins].
Epstein-Barr virus (EBV) infects human B lymphocytes and efficiently transforms them into immortalized lymphoblasts. EBV-determined nuclear antigen (EBNA) and EBV latent infection membrane protein (LMP) are expressed in latently infected, growth-transformed lymphoblasts. To elucidate the functions of EBNA and LMP, clones of cells were established that stably expressed EBNA-1, EBNA-2, EBNA-3A, EBNA-leader protein (EBNA-Lp) or LMP, using gene transfer technique and the growth characteristics of the transfectants were examined. The expression of EBNA-1, EBNA-2,EBNA-3A,EBNA-Lp or LMP caused shortening of doubling time, increased saturation cell density, reduced serum dependence, anchorage-independent growth in semisolid agar and activation of c-myc. Furthermore, the expression of LMP in NIH/3T3 cells led to tumorigenicity in nude mice, enhanced expression of H-ras and increased production of diacylglycerol, which might activate protein kinase C. B cell line, BJAB, EBNA-1 was responsible for expression of c-fgr mRNA and EBNA -2 specifically induced expression of B-cell activation antigens, including CD21 (CR2) and CD23 (Fc epsilon receptor). These results indicate that EBNA and LMP play an important role in EBV-induced growth transformation. It is possible that EBNA-1 and EBNA-2 are directly involved in the early process of immortalization. It is also possible that LMP could contribute to tumorigenic alteration of immortalized cells. The proliferation of the EBNA or LMP-expressing cells was markedly enhanced by phorbol ester. By contrast phorbol ester had no effect on the proliferation of nonexpressing control cells. The phorbol ester enhancement of EBV-induced growth transformation is likely to be mediated by EBNA and LMP.
Kinoshita
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Department of Virology, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D001402:B-Lymphocytes / Q000473:pathology*; D002472:Cell Transformation, Viral / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D019309:Epstein-Barr Virus Nuclear Antigens; D015967:Gene Expression Regulation, Viral; D016259:Genes, myc; D011905:Genes, ras; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology
D000956:Antigens, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D008565:Membrane Proteins; D010703:Phorbol Esters; D004247:DNA