LYMPHOBLASTOID-CELLS TRANSFECTED WITH C-MYC - DOWN-REGULATION OF EBV-LYTIC ANTIGENS AND IMPAIRED RESPONSE OF AUTOLOGOUS CD4(-CELLS IN-VITRO() T)

Normal EBV-positive lymphoblastoid B-cell lines (LCL) were transfected with vectors containing the c-myc oncogene (pHEBO-E mu-myc) or contro l vectors (pHEBO-E mu) and analyzed for the expression of EBV-lytic an d latent antigens. While EBV-latent antigens were normal in the c-myc transfectants, there was an almost complete downregulation of EBV-lyti c antigens, including BZLF1, EA(D), gp340 and VCA. These observations were consistently repeated on 6 different LCLs transfected with c-myc. Unlike control LCLs, the c-myc transfectants did not release infectio us EBV. PCR analysis demonstrated that BZLF1 mRNA was virtually absent in c-myc transfectants, possibly suggesting that the deregulated c-my c imposed a block in the EBV-lytic cycle at this particular level. c-m yc transfectants failed to sustain the prliferative response of autolo gous CD4(+) T-cell clones with specificity far EBV-lytic antigens. How ever, they regained this capacity after incubation with ultraviolet-in activated EBV or gp340 antigen in vitro, also indicating that their an tigen-presenting capacities were not impaired. c-myc transfectants fai led to elicit a secondary proliferative response by autologous CD4(+) T cells purified from the peripheral blood of EBV-seropositive donors. Exposure of c-myc transfectants to W-inactivated EBV again resulted i n a proliferative CD4(+)-T-cell response comparable to that elicited b y the control LCLs. Collectively, our data provide evidence for the re markable ability of an oncogene to influence the life cycle of a virus and to modify the antigenicity of the infected cells. (C) 1996 Wiley- Liss, Inc.