BZLF1 transcript variants in Epstein-Barr virus-positive epithelial cell lines.

Abstract

Epstein-Barr virus (EBV) is a widely prevalent pathogen currently infecting over 90% of the human population and is associated with various lymphomas and carcinomas. Lytic replication of EBV is regulated by the expression of the immediate-early genes BZLF1 and BRLF1. In B lymphocytes, BZLF1 transcripts have been shown to be processed to a fully spliced form, as well as zDelta, a spliced variant containing only the first and third exons. While splice variants have been reported in nasopharyngeal carcinoma biopsies, alternative splicing of BZLF1 in EBV-positive epithelial cell lines has not yet been characterized. In this study, we identified the consistent expression of three distinct BZLF1 transcripts in the EBV-positive epithelial cell lines D98/HR1, AGS-BDneo, and AGS-BX1. These BZLF1 transcripts consisted of not only the normally spliced variant but also a completely unspliced and a spliced variant containing exons one and three only. In contrast, we detected only the normally spliced version of the BZLF1 transcript in B-cell lines (B95-8, IM-9, Raji and Daudi). Previous work has also demonstrated that inhibition of the mTOR pathway, via rapamycin, altered total levels of BZLF1 transcripts. We examined the production of specific transcript variants under rapamycin treatment and found that rapamycin alters the production of transcripts in a cell-type, as well as transcripts in variant-type, manners. The expression of these transcript variants may play a role in modulating the replication cycle of EBV within epithelial cells.