Antisense to Epstein Barr Virus-encoded LMP1 does not affect the transcription of viral and cellular proliferation-related genes, but induces phenotypic effects on EBV-transformed B lymphocytes

• Published in: Oncogene Vol. 21; no. 26; pp. 4166 - 4170
• Main Authors: Masciarelli, Silvia, Mattioli, Benedetta, Galletti, Roberta, Samoggia, Paola, Chichiarelli, Silvia, Mearini, Giulia, Mattia, Elena
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 13.06.2002
• Subjects: Antigens; Antisense oligonucleotides; Antisense therapy; Apoptosis; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Base Sequence; Bcl-2 protein; CD23 antigen; Cell Division - genetics; Cell growth; Cell Line, Transformed; Cell proliferation; DNA Primers; Epstein-Barr virus; Gene expression; Genes, Viral; Genotype & phenotype; Health sciences; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - physiology; Immortalization; Immunophenotyping; LMP1 protein; Lymphocytes; Lymphocytes B; Lymphoma; Mcl-1 protein; Oligomers; Oligonucleotides, Antisense - pharmacology; Phenotypes; Public health; Transcription; Transcription, Genetic - drug effects; Tumor Cells, Cultured; Tumors; Viral Matrix Proteins - genetics; Viruses; Rome Italy; Italy
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1205515

It is generally accepted that Epstein-Barr virus (EBV) latent genes EBNA-2, EBNA-3A, -3C, EBNA-LP and LMP1 are essential for growth transformation and immortalization of B lymphocytes. Among these genes, LMP1 plays a key role in the survival and dissemination of the infected B cells by inducing anti-apoptotic genes and surface expression of several activation antigens and adhesion molecules. We have previously shown that antisense oligodeoxynucleotides directed to LMP1 mRNA, effectively suppress LMP1 gene expression and substantially reduce B95.8 cell proliferation. In this study, we have used antisense LMP1 oligomers to investigate whether LMP1 suppression might influence the expression of latent EBV genes with oncogenic potential, anti-apoptotic genes, or affect the phenotype of EBV-infected B95.8 cells. Our data show that LMP1 suppression does not affect the transcription of EBNA-2, EBNA-3A, -3B and -3C genes, or that of bcl-2 and mcl-1 anti-apoptotic genes. In contrast, consistent modifications in the expression of CD39, CD54, CD23, CD11 and CD10 molecules were observed in B95.8 cells after treatment with antisense LMP1. Our findings support the possibility for using LMP1 antisense oligomers as therapeutics in EBV-associated tumors.