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Journal of Virology, July 2007, p. 7363-7370, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00154-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

X-Box-Binding Protein 1 Activates Lytic Epstein-Barr Virus Gene Expression in Combination with Protein Kinase D{triangledown}

Prasanna M. Bhende,1 Sarah J. Dickerson,2 Xiaoping Sun,2 Wen-Hai Feng,1 and Shannon C. Kenney1,2*

Departments of Medicine and Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,1 Departments of Medicine and Oncology, University of Wisconsin at Madison, Madison, Wisconsin2

Received 23 January 2007/ Accepted 2 May 2007

Epstein-Barr virus (EBV) establishes a latent form of infection in memory B cells, while antibody-secreting plasma cells often harbor the lytic form of infection. The switch between latent and lytic EBV infection is mediated by the two viral immediate-early proteins BZLF1 (Z) and BRLF1 (R), which are not expressed in latently infected B cells. Here we demonstrate that a cellular transcription factor that plays an essential role in plasma cell differentiation, X-box-binding protein 1 (XBP-1), also activates the transcription of the two EBV immediate-early gene promoters. In reporter gene assays, XBP-1 alone was sufficient to activate the R promoter, whereas the combination of XBP-1 and protein kinase D (PKD) was required for efficient activation of the Z promoter. Most importantly, the expression of XBP-1 and activated PKD was sufficient to induce lytic viral gene expression in EBV-positive nasopharyngeal carcinoma cells and lymphoblastoid cells, while an XBP-1 small interfering RNA inhibited constitutive lytic EBV gene expression in lymphoblastoid cells. These results suggest that the plasma cell differentiation factor XBP-1, in combination with activated PKD, can mediate the reactivation of EBV, thereby allowing the viral life cycle to be intimately linked to plasma cell differentiation.

* Corresponding author. Mailing address: Departments of Medicine and Oncology, 421A McArdle, 1400 University Ave., Madison, WI 53706. Phone: (608) 261-1196. Fax: (608) 262-2824. E-mail: skenney{at}wisc.edu

{triangledown} Published ahead of print on 9 May 2007.

Journal of Virology, July 2007, p. 7363-7370, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00154-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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