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Lymphoblastoid cells transfected with c‐ myc : Downregulation of EBV‐lytic antigens and impaired response of autologousCD4 + T cells in vitro
Author(s) -
Fais Franco,
Cutrona Giovanna,
Ulivi Massimo,
Roncella Silvio,
Gagliardi M. Cristina,
CornagliaFerraris Paolo,
Rowe Martin,
Barnaba Vincenzo,
Ferrarini Manlio
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19961211)68:6<810::aid-ijc20>3.0.co;2-2
Subject(s) - lytic cycle , bzlf1 , antigen , biology , epstein–barr virus , transfection , virology , microbiology and biotechnology , downregulation and upregulation , in vitro , lymphoblast , virus , cell culture , immunology , herpesviridae , gene , viral disease , biochemistry , genetics
Normal EBV‐positive lymphoblastoid B‐cell lines (LCL) were transfected with vectors containing the c‐ myc oncogene (pHEBO‐Eμ‐ myc ) or control vectors (pHEBO‐Eμ) and analyzed for the expression of EBV‐lytic and latent antigens. While EBV‐latent antigens were normal in the c‐ myc transfectants there was an almost complete downregulation of EBV‐lytic antigens, including BZLFI, 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 infectious EBV. PCR analysis demonstrated that BZLFI mRNA was virtually absent in c‐ myc transfectants, possibly suggesting that the deregulated c‐ myc imposed a block in the EBV‐lytic cycle at this particular level. c‐ myc transfectants failed to sustain the proliferative response of autologous CD4 + T‐cell clones with specificity for EBV‐lytic antigens. However, they regained this capacity after incubation with ultraviolet‐inactivated EBV or gp340 antigen in vitro , also indicating that their antigen‐presenting capacities were not impaired. c‐ myc transfectants failed 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 UV‐inactivated EBV again resulted in a proliferative CD4 + T‐cell response comparable to that elicited by the control LCLs. Collectively, our data provide evidence for the remarkable ability of an oncogene to influence the life cycle of a virus and to modify the antigenicity of the infected cells. © 1996 Wiley‐Liss, Inc.