Roles of Epstein-Barr virus encoded RNAs during EBV latent infection

Abstract

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that establishes lifelong latent infection in B lymphocytes. It is known to contribute to several malignancies including Burkitt's lymphoma (BL), Hodgkin's lymphoma, and nasopharyngeal carcinoma. EBV produces two non-coding RNAs, EBERs (Epstein-Barr encoded RNAs) 1 and 2, which are the most abundant viral transcripts in latent infection. EBER1 and EBER2 are expressed at high levels in almost all cells of EBV-associated malignancies and have been reported to contribute to the oncogenic phenotype of EBV-positive BL. Recent microarray analysis of lymphoblastoid cell lines (LCLs) containing EBER deletion mutants of EBV has identified several genes whose expression changes in response to deletion of EBER1 or EBER2. EBERs have also been recently shown to induce interferon alpha during the first three days of EBV infection. Therefore gene expression in B cells was investigated during early EBV infection, using recombinant EBER knockout EBV strains, with a focus on microarray targets and interferon alpha genes. The study showed that expression changes in the target genes did not occur directly following infection, indicating that expression changes previously identified were the downstream result of complex processes. The other method developed to investigate roles of the EBERs was the introduction of EBER expression into EBER negative cell lines using a lentiviral vector-based approach. This will enable stable EBER-expression in a variety of cell lines once the variability in EBER expression has been improved.