Interferon regulatory factor 2 represses the Epstein-Barr virus BamHI Q latency promoter in type III latency

Luwen Zhang, Joseph S. Pagano

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is the essential protein from maintenance of the EBV episome and establishment of latency. The BamHI Q promoter (Qp) is used for the transcription of EBNA-1 mRNA in type I and type II latency, which are EBV infection states exemplified by Burkitt's lymphoma and nasopharyngeal carcinoma. However, Qp is inactive in type III latency, and other promoters (the BamHI C promoter and/or the BamHI W promoter) are used for EBNA-1. The involvement of interferon regulatory factors (IRFs) in the regulation of Qp is suggested by the presence of an essential interferon-stimulated response element (ISRE) in the promoter. In this work, expression of IRF-2 is shown to be inversely associated with Qp status, i.e., IRF-2 levels are high in type III latency (when Qp is inactive) and low in type I latency (when Qp is active). Also, IRF-2 is identified by electrophoretic mobility shift assay as the major protein binding to the Qp ISRE in type III latency. In transient transfection assays, IRF-2 represses activity of Qp-reporter constructs. Overexpression of IRF-2 in a type I latency cell line did not activate the endogenous Qp but marginally reduced the EBNA-1 mRNA level. Switching from type III latency (Qp inactive) to type II latency (Qp active), as produced by cell fusion, is directly associated with greatly reduced expression of IRF-2. These data strongly suggest that IRF-2 is a negative regulator Qp and may contribute to the silencing of Qp in type III latency.

Original languageEnglish (US)
Pages (from-to)3216-3223
Number of pages8
JournalMolecular and cellular biology
Volume19
Issue number4
DOIs
StatePublished - Jan 1 1999

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Interferon Regulatory Factor-2
Human Herpesvirus 4
Epstein-Barr Virus Nuclear Antigens
Response Elements
Interferons
Interferon Regulatory Factors
Messenger RNA
Epstein-Barr Virus Infections
Burkitt Lymphoma
Cell Fusion
Electrophoretic Mobility Shift Assay
Protein Binding
Transfection
Plasmids
Maintenance
Cell Line

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Interferon regulatory factor 2 represses the Epstein-Barr virus BamHI Q latency promoter in type III latency. / Zhang, Luwen; Pagano, Joseph S.

In: Molecular and cellular biology, Vol. 19, No. 4, 01.01.1999, p. 3216-3223.

Research output: Contribution to journalArticle

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