LMP1

LMP1 is the acronym for "latent membrane protein 1", which is the primary transforming gene product of the Epstein-Barr virus (EBV). LMP1 is expressed in most EBV-associated lymphoproliferative diseases and malignancies and contributes significantly to pathogenesis and disease phenotypes. It is a viral oncoprotein that plays a key role in the transformation of infected cells and contributes to the development of certain cancers, including nasopharyngeal carcinoma and Hodgkin's lymphoma.

LMP1 has a high potential to deregulate cellular signal transduction pathways, leading to proliferation of target cells and simultaneous subversion of cell death programs.

By behaving like a constitutively active receptor, LMP1 recruits cellular signaling molecules associated with tumor necrosis factor receptors, such as tumor necrosis factor receptor-associated factor (TRAF) proteins and TRADD, to mimic signals from the costimulatory CD40 receptor in EBV-infected B lymphocytes. LMP1 activates the signaling pathways NF-κB, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3-K), IRF7 and STAT.

LMP1 also has multiple functions, ranging from the induction of cytokines and chemokines, immunomodulation, global alteration of gene and microRNA expression patterns to the regulation of tumor angiogenesis, cell-cell contact, cell migration and invasive growth of tumor cells.

Several latent EBV genes are thought to interact in the immortalization of B cells. LMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A, is capable of transforming human primary B cells. LMP1/EBNA2-immortalized cell lines share surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They show sustained growth for more than 60 days (Zhang J et al. 2023).

1. Huang J et al. (2024) Assembly and activation of EBV latent membrane protein 1. Cell 187:4996-5009.e14.
2. Zhang J et al. (2023) LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells. Front Immunol 14:1331730.