Characterization of a Suppressive Cis-acting Element in the Epstein–Barr Virus LMP1 Promoter

• Main Authors: Masahiro Yoshida, Takayuki Murata, Keiji Ashio, Yohei Narita, Takahiro Watanabe, H. M. Abdullah Al Masud, Yoshitaka Sato, Fumi Goshima, Hiroshi Kimura
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-11-01
• Series: Frontiers in Microbiology
• Subjects: EBV; LMP1; promoter; transcription; EBV-BAC
• Online Access: http://journal.frontiersin.org/article/10.3389/fmicb.2017.02302/full

Latent membrane protein 1 (LMP1) is a major oncogene encoded by Epstein–Barr virus (EBV) and is essential for immortalization of B cells by the virus. Previous studies suggested that several transcription factors, such as PU.1, RBP-Jκ, NFκB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however, the means by which the oncogene is negatively regulated remains unclear. Here, we introduced short mutations into the proximal LMP1 promoter that includes recognition sites for the E-box and Ikaros transcription factors in the context of EBV-bacterial artificial chromosome. Upon infection, the mutant exhibited increased LMP1 expression and EBV-mediated immortalization of B cells. However, single mutations of either the E-box or Ikaros sites had limited effects on LMP1 expression and transformation. Our results suggest that this region contains a suppressive cis-regulatory element, but other transcriptional repressors (apart from the E-box and Ikaros transcription factors) may remain to be discovered.