Regulation of Interleukin-1β Transcription by Epstein–Barr Virus Involves a Number of Latent Proteins via Their Interaction with RBP

• Published in: Virology (New York, N.Y.) N.Y.), 1998-12, Vol.252 (2), p.418-430
• Main Authors: Krauer, Kenia G., Belzer, Deanna K., Liaskou, Daphne, Buck, Marion, Cross, Simone, Honjo, Tasuku, Sculley, Tom
• Format: Article
• Language: English
• Subjects: Epstein-Barr virus
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1998.9441

Epstein–Barr virus (EBV) infects B cells, resulting in the outgrowth of immortalised lymphoblastoid cell lines (LCLs). Here, we demonstrate through the use of intracellular staining that interleukin-1β (IL-1β) is expressed in LCLs and investigate the influence of the individual latent proteins on the expression of IL-1β. Using RT-PCR, IL-1β was shown to be up-regulated in EBV-transformed LCLs as well as in group III Burkitt's lymphoma (BL) cell lines, compared with group I BL cell lines. The up-regulation of IL-1β message could be mediated by the latent membrane protein-1, EBV nuclear proteins 2, 3, 4, and 6 genes. Electrophoretic mobility shift assays (EMSAs) demonstrated that the −300 region of the IL-1β promoter, which contains a nuclear factor-κB (NF-κB) binding site, contained a functional RBP binding site. Binding of RBP to this site could be inhibited by addition of EBV nuclear proteins 3 and 6, suggesting that these proteins displace RBP from its recognition sequence, removing transcriptional repression and allowing gene transcription to occur. In group I BL cells, containing low levels of NF-κB, only RBP binding was observed in EMSAs, whereas NF-κB binding could be demonstrated in EBV-transformed B cell lines containing high levels of activated NF-κB. In addition, the expression of latent membrane protein-1 led to activation of NF-κB that was capable of binding the IL-1β promoter. The study demonstrates that EBV can up-regulate IL-1β expression, possibly by using RBP, NF-κB, or both.