X-box binding protein 1 induces the expression of the lytic cycle transactivator of Kaposi's sarcoma-associated herpesvirus but not Epstein Barr virus in co-infected primary effusion lymphoma

Title: X-box binding protein 1 induces the expression of the lytic cycle transactivator of Kaposi's sarcoma-associated herpesvirus but not Epstein Barr virus in co-infected primary effusion lymphoma
Authors: Lai, IY-C
Farrell, PJ
Kellam, P
Item Type: Journal Article
Abstract: Cells of primary effusion lymphoma (PEL), a B-cell non-Hodgkin's lymphoma, are latently infected by Kaposi's sarcoma-associated herpesvirus (KSHV), with about 80 % of PEL also co-infected with Epstein–Barr virus (EBV). Both viruses can be reactivated into their lytic replication cycle in PEL by chemical inducers. However, simultaneous activation of both lytic cascades leads to mutual lytic cycle co-repression. The plasma cell-differentiation factor X-box binding protein 1 (XBP-1) transactivates the KSHV immediate–early promoter leading to the production of the replication and transcription activator protein (RTA), and reactivation of KSHV from latency. XBP-1 has been reported to act similarly on the EBV immediate–early promoter Zp, leading to the production of the lytic-cycle transactivator protein BZLF1. Here we show that activated B-cell terminal-differentiation transcription factor X-box binding protein 1 (XBP-1s) does not induce EBV BZLF1 and BRLF1 expression in PEL and BL cell lines, despite inducing lytic reactivation of KSHV in PEL. We show that XBP-1s transactivates the KSHV RTA promoter but does not transactivate the EBV BZLF1 promoter in non-B-cells by using a luciferase assay. Co-expression of activated protein kinase D, which can phosphorylate and inactivate class II histone deacetylases (HDACs), does not rescue XBP-1 activity on Zp nor does it induce BZLF1 and BRLF1 expression in PEL. Finally, chemical inducers of KSHV and EBV lytic replication in PEL, including HDAC inhibitors, do not lead to XBP-1 activation. We conclude that XBP-1 specifically reactivates the KSHV lytic cycle in dually infected PELs.
Issue Date: 1-Feb-2011
Date of Acceptance: 22-Oct-2010
URI: http://hdl.handle.net/10044/1/69471
DOI: https://dx.doi.org/10.1099/vir.0.025494-0
ISSN: 1465-2099
Publisher: Microbiology Society
Start Page: 421
End Page: 431
Journal / Book Title: Journal of General Virology
Volume: 92
Copyright Statement: © 2011 SGM. This is an open access article published by the Microbiology Society under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology
Life Sciences & Biomedicine
Biotechnology & Applied Microbiology
Virology
PLASMA-CELL DIFFERENTIATION
MEMORY B-CELLS
SIGNAL-TRANSDUCTION
GENE-EXPRESSION
KINASE-C
IN-VIVO
TERMINAL DIFFERENTIATION
FACTOR XBP-1
LATENCY
EBV
Cell Line, Tumor
DNA-Binding Proteins
Gene Expression Regulation, Viral
Herpesvirus 4, Human
Herpesvirus 8, Human
Humans
Lymphoma, Primary Effusion
Regulatory Factor X Transcription Factors
Trans-Activators
Transcription Factors
Viral Proteins
X-Box Binding Protein 1
06 Biological Sciences
07 Agricultural and Veterinary Sciences
11 Medical and Health Sciences
Publication Status: Published
Appears in Collections:Department of Medicine



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