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The B-cell specific transcription factor, Oct-2, promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein, BZLF1.
PLoS Pathog. 2012 Feb; 8(2):e1002516.PP

Abstract

The Epstein-Barr virus (EBV) latent-lytic switch is mediated by the BZLF1 immediate-early protein. EBV is normally latent in memory B cells, but cellular factors which promote viral latency specifically in B cells have not been identified. In this report, we demonstrate that the B-cell specific transcription factor, Oct-2, inhibits the function of the viral immediate-early protein, BZLF1, and prevents lytic viral reactivation. Co-transfected Oct-2 reduces the ability of BZLF1 to activate lytic gene expression in two different latently infected nasopharyngeal carcinoma cell lines. Furthermore, Oct-2 inhibits BZLF1 activation of lytic EBV promoters in reporter gene assays, and attenuates BZLF1 binding to lytic viral promoters in vivo. Oct-2 interacts directly with BZLF1, and this interaction requires the DNA-binding/dimerization domain of BZLF1 and the POU domain of Oct-2. An Oct-2 mutant (Δ262-302) deficient for interaction with BZLF1 is unable to inhibit BZLF1-mediated lytic reactivation. However, an Oct-2 mutant defective for DNA-binding (Q221A) retains the ability to inhibit BZLF1 transcriptional effects and DNA-binding. Importantly, shRNA-mediated knockdown of endogenous Oct-2 expression in several EBV-positive Burkitt lymphoma and lymphoblastoid cell lines increases the level of lytic EBV gene expression, while decreasing EBNA1 expression. Moreover, treatments which induce EBV lytic reactivation, such as anti-IgG cross-linking and chemical inducers, also decrease the level of Oct-2 protein expression at the transcriptional level. We conclude that Oct-2 potentiates establishment of EBV latency in B cells.

Authors+Show Affiliations

Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22346751

Citation

Robinson, Amanda R., et al. "The B-cell Specific Transcription Factor, Oct-2, Promotes Epstein-Barr Virus Latency By Inhibiting the Viral Immediate-early Protein, BZLF1." PLoS Pathogens, vol. 8, no. 2, 2012, pp. e1002516.
Robinson AR, Kwek SS, Kenney SC. The B-cell specific transcription factor, Oct-2, promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein, BZLF1. PLoS Pathog. 2012;8(2):e1002516.
Robinson, A. R., Kwek, S. S., & Kenney, S. C. (2012). The B-cell specific transcription factor, Oct-2, promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein, BZLF1. PLoS Pathogens, 8(2), e1002516. https://doi.org/10.1371/journal.ppat.1002516
Robinson AR, Kwek SS, Kenney SC. The B-cell Specific Transcription Factor, Oct-2, Promotes Epstein-Barr Virus Latency By Inhibiting the Viral Immediate-early Protein, BZLF1. PLoS Pathog. 2012;8(2):e1002516. PubMed PMID: 22346751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The B-cell specific transcription factor, Oct-2, promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein, BZLF1. AU - Robinson,Amanda R, AU - Kwek,Swee Sen, AU - Kenney,Shannon C, Y1 - 2012/02/09/ PY - 2011/08/11/received PY - 2011/12/16/accepted PY - 2012/2/21/entrez PY - 2012/2/22/pubmed PY - 2014/7/10/medline SP - e1002516 EP - e1002516 JF - PLoS pathogens JO - PLoS Pathog VL - 8 IS - 2 N2 - The Epstein-Barr virus (EBV) latent-lytic switch is mediated by the BZLF1 immediate-early protein. EBV is normally latent in memory B cells, but cellular factors which promote viral latency specifically in B cells have not been identified. In this report, we demonstrate that the B-cell specific transcription factor, Oct-2, inhibits the function of the viral immediate-early protein, BZLF1, and prevents lytic viral reactivation. Co-transfected Oct-2 reduces the ability of BZLF1 to activate lytic gene expression in two different latently infected nasopharyngeal carcinoma cell lines. Furthermore, Oct-2 inhibits BZLF1 activation of lytic EBV promoters in reporter gene assays, and attenuates BZLF1 binding to lytic viral promoters in vivo. Oct-2 interacts directly with BZLF1, and this interaction requires the DNA-binding/dimerization domain of BZLF1 and the POU domain of Oct-2. An Oct-2 mutant (Δ262-302) deficient for interaction with BZLF1 is unable to inhibit BZLF1-mediated lytic reactivation. However, an Oct-2 mutant defective for DNA-binding (Q221A) retains the ability to inhibit BZLF1 transcriptional effects and DNA-binding. Importantly, shRNA-mediated knockdown of endogenous Oct-2 expression in several EBV-positive Burkitt lymphoma and lymphoblastoid cell lines increases the level of lytic EBV gene expression, while decreasing EBNA1 expression. Moreover, treatments which induce EBV lytic reactivation, such as anti-IgG cross-linking and chemical inducers, also decrease the level of Oct-2 protein expression at the transcriptional level. We conclude that Oct-2 potentiates establishment of EBV latency in B cells. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/22346751/The_B_cell_specific_transcription_factor_Oct_2_promotes_Epstein_Barr_virus_latency_by_inhibiting_the_viral_immediate_early_protein_BZLF1_ L2 - https://dx.plos.org/10.1371/journal.ppat.1002516 DB - PRIME DP - Unbound Medicine ER -