Pathogens 2012, 1(2), 83-101; doi:10.3390/pathogens1020083
Article

Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas

1,2,†,* email, 1,†email, 3email, 1email, 1email, 2email, 4email, 1email, 3email and 1,2email
Received: 15 August 2012; in revised form: 19 September 2012 / Accepted: 24 September 2012 / Published: 8 October 2012
(This article belongs to the Special Issue Infection and Cancer)
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Abstract: B-lymphocyte-induced maturation protein 1 (BLIMP1) exists as two major isoforms, α and β, which arise from alternate promoters. Inactivation of the full length BLIMP1α isoform is thought to contribute to B cell lymphomagenesis by blocking post-germinal centre (GC) B cell differentiation. In contrast, the shorter β isoform is functionally impaired and over-expressed in several haematological malignancies, including diffuse large B cell lymphomas (DLBCL). We have studied the influence on BLIMP1β expression of the Epstein-Barr virus (EBV), a human herpesvirus that is implicated in the pathogenesis of several GC-derived lymphomas, including a subset of DLBCL and Hodgkin’s lymphoma (HL). We show that BLIMP1β expression is increased following the EBV infection of normal human tonsillar GC B cells. We also show that this change in expression is accompanied by hypomethylation of the BLIMP1β-specific promoter. Furthermore, we confirmed previous reports that the BLIMP1β promoter is hypomethylated in DLBCL cell lines and show for the first time that BLIMP1β is hypomethylated in the Hodgkin/Reed-Sternberg (HRS) cells of HL. Our results provide evidence in support of a role for BLIMP1β in the pathogenesis of EBV-associated B cell lymphomas.
Keywords: BLIMP1; Epstein-Barr virus; hypomethylation; Hodgkin’s lymphoma
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Vrzalikova, K.; Leonard, S.; Fan, Y.; Bell, A.; Vockerodt, M.; Flodr, P.; Wright, K.L.; Rowe, M.; Tao, Q.; Murray, P.G. Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas. Pathogens 2012, 1, 83-101.

AMA Style

Vrzalikova K, Leonard S, Fan Y, Bell A, Vockerodt M, Flodr P, Wright KL, Rowe M, Tao Q, Murray PG. Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas. Pathogens. 2012; 1(2):83-101.

Chicago/Turabian Style

Vrzalikova, Katerina; Leonard, Sarah; Fan, Yichao; Bell, Andrew; Vockerodt, Martina; Flodr, Patrik; Wright, Kenneth L.; Rowe, Martin; Tao, Qian; Murray, Paul G. 2012. "Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas." Pathogens 1, no. 2: 83-101.

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