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Journal of Virology, February 2002, p. 1914-1921, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1914-1921.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Saparna Pai,1 Brendan J. O'Sullivan,2 Leanne Cooper,1 Ranjeny Thomas,2 and Rajiv Khanna1*

Tumour Immunology Laboratory, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research and Joint Oncology Program, University of Queensland, Brisbane, Queensland 4029,1 Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Brisbane, Queensland 4102, Australia2

Received 24 July 2001/ Accepted 12 November 2001

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.

* Corresponding author. Mailing address: Queensland Institute of Medical Research, Bancroft Centre, 300 Herston Rd., Brisbane, Australia 4029. Phone: 61-7-3362-0346. Fax: 61-7-3362-0106. E-mail: rajivK{at}qimr.edu.au.

Journal of Virology, February 2002, p. 1914-1921, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1914-1921.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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