RelB nuclear translocation mediated by C-terminal activator regions of Epstein-Barr virus-encoded latent membrane protein 1 and its effect on antigen-presenting function in B cells.

Abstract

Previous studies have shown that Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) is uniquely able to up-regulate the expression of the peptide transporters (referred to as TAP-1 and TAP-2) and major histocompatibility complex (MHC) class I in Burkitt's lymphoma (BL) cell lines. This up-regulation is often accompanied by a restoration of antigen-presenting function as measured by the ability of these cells to present endogenously expressed viral antigen to cytotoxic T lymphocytes. Here we show that the expression of LMP1 resulted in up-regulation and nuclear translocation of RelB that were coincident with increased expression of MHC class I in BL cells. Deletion of the C-terminal activator regions (CTARs) of LMP1 significantly impaired the abilities of LMP1 to translocate RelB into the nucleus and to up-regulate the expression of antigen-processing genes. Further analysis with single-point mutations within the CTARs confirmed that the residues critical for NF-kappa B activation directly contribute to antigen-processing function regulation in BL cells. This LMP1-mediated effect was blocked following expression of either dominant negative I kappa B alpha S32/36A, an NF-kappa B inhibitor, or antisense RelB. These observations indicate that upregulation of antigen-presenting function in B cells mediated by LMP1 is signaled through the NF-kappa B subunit RelB. The data provide a mechanism by which LMP1 modulates immunogenicity of Epstein-Barr virus-infected normal and malignant cells.

• Authors: Saparna Pai, Brendan J O'Sullivan, Leanne Cooper, Ranjeny Thomas, Rajiv Khanna
• Journal: Journal of virology (J Virol) Vol. 76 Issue 4 Pg. 1914-21 (Feb 2002) ISSN: 0022-538X [Print] United States
• PMID: 11799186 (Publication Type: Journal Article)

Chemical References

• EBV-associated membrane antigen, Epstein-Barr virus
• NF-kappa B
• Proto-Oncogene Proteins
• RELB protein, human
• Transcription Factors
• Viral Matrix Proteins
• Transcription Factor RelB

Topics

• Active Transport, Cell Nucleus
• Antigen Presentation (genetics, physiology)
• B-Lymphocytes (immunology, virology)
• Burkitt Lymphoma (virology)
• Cell Line, Transformed
• Cell Nucleus (metabolism)
• Epstein-Barr Virus Infections (virology)
• Gene Expression Regulation, Viral
• Herpesvirus 4, Human (genetics, physiology)
• Humans
• NF-kappa B (genetics, metabolism)
• Proto-Oncogene Proteins (genetics, metabolism)
• Transcription Factor RelB
• Transcription Factors (genetics, metabolism)
• Tumor Cells, Cultured
• Viral Matrix Proteins (chemistry, genetics, metabolism)