Epstein-Barr virus nuclear protein 2-induced activation of the EBV-replicative cycle in Akata cells: analysis by tetracycline-regulated expression.

Abstract

Epstein-Barr virus has a unique ability to transform human B cells into activated lymphoblasts and establish lymphoblastoid cell lines (LCLs) with infinite proliferative potential in vitro (for review, see Kieff 1996). This process, termed growth transformation or immortalization, is supposed to be a prerequisite for the virus’ ability to establish life-long persistent infection in humans. Since similar signal pathways are activated and similar genes are induced in both EBV-mediated immortalization and antigen-induced activation, it is generally considered that EBV utilizes the normal mechanism of antigen-induced activation to immortalize B lymphocytes. In EBV-immortalized lymphoblastoid cells, viral DNA persists as circular episomes, and 11 viral genes are expressed. This program of EBV gene expression is called latency III (for review, see Rickinson and Kieff 1996). Six of the eleven genes code for EBV nuclear proteins (EBNAs 1, 2, 3A, 3B, 3C, and LP) and three for latent membrane proteins (LMPs 1, 2A, and 2B). The remaining two genes code for the EBV-encoded small RNAs (EBERs 1 and 2), that are not translated into proteins. In addition, a family of extensively spliced messenger (m)RNAs containing the BARF0 open reading frame are transcribed from a region including the BamHl A fragment, but their protein products have not been definitely identified. Genetic analyses using recombinant EBVs so far showed that EBNA2, EBNA3A, EBNA3C, and LMP1 are essential for lymphocyte immortalization Kieff 1996). EBNA1 is required for intracellular persistence of EBV DNA in a plasmid form.KeywordsLatent Membrane ProteinEBNA2 GeneAkata CellConstitutive Expression VectorLymphocyte ImmortalizationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.