Epstein-Barr viral nuclear antigen 1 antisense oligodeoxynucleotide inhibits proliferation of Epstein-Barr virus-immortalized B cells.
The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is a latent viral protein that is expressed in all EBV-immortalized lymphocytes and plays an essential role in immortalization y EBV. EBNA-1 protein is required for replication and maintenance of the episomal viral genome in latently infected, immortalized cells. Given the essential function of EBNA-1 in immortalization, we have examined the effect of EBNA-1 antisense oligodeoxynucleotides on expression of EBNA-1 protein and proliferation in EBV-immortalized lymphoblastoid cells. We have shown that exposure to unmodified antisense oligodeoxynucleotide of codons 6 through 10 of EBNA-1 partially suppressed EBNA-1 protein expression in EBV-immortalized lymphoblastoid cells relative to untreated cells or cells exposed to two scrambled sequences of the EBNA-1 antisense. Furthermore, EBNA-1 antisense inhibited proliferation of EBV-immortalized cells by at least 50% compared with the scrambled antisense sequences. There was no difference in the effect of antisense and scrambled antisense oligodeoxynucleotides on the proliferation of EBV-negative cells, indicating that the antiproliferative effect of EBNA-1 antisense was EBV-specific. These findings underscore the essential role of EBNA-1 in immortalization and, furthermore, have potential therapeutic implications for EBV-associated neoplastic diseases.
University of Colorado Health Sciences Center, Denver.
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Roth
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Curiel
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Lacy
D000328:Adult; D000956:Antigens, Viral / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology*; D001483:Base Sequence; D002460:Cell Line; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000502:physiology*; D019309:Epstein-Barr Virus Nuclear Antigens; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D016376:Oligonucleotides, Antisense