Interferon regulatory factor 7 is induced by Epstein-Barr virus latent membrane protein 1

Luwen Zhang, Joseph S. Pagano

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Infection by Epstein-Barr virus (EBV) generates several types of latency with different profiles of gene expression but with expression of Epstein- Barr nuclear antigen 1 (EBNA-1) in common. The BamHI Q promoter (Qp) is used for the transcription of EBNA-1 mRNA in type I latency, which is an EBV infection state exemplified by Burkitt's lymphoma (BL). However, Qp is inactive in type III latency, and other promoters (C/Wp) are used for transcription of EBNA-1, which raises the question of how usage of these promoters is governed. Interferon (IFN) regulatory factor 7 (IRF-7) was identified first as a negative regulator of Qp. Expression of IRF-7 is associated with EBV type HI latency, where Qp is inactive, but not with type I latency, raising the possibility that a viral gene product(s) expressed in type III latency might induce IRF-7 and repress Qp. Here, detailed analysis of the expression of IRF-7 revealed that it is associated with the expression of EBV latent membrane protein 1 (LMP-1) and that LMP-1 stimulates the expression of IRF-7 in type III latency in which Qp is inactive. In contrast, LMP-1 is not expressed in type I latency cells in which Qp is active. LMP-1 represses the constitutive activity of Qp reporter constructs. Mutational analysis of Qp reporter constructs revealed that the Qp IFN-stimulated response element (ISRE) is essential for the repression by LMP-1. Furthermore, LMP-1 reduced EBNA-1 mRNA derived from Qp only in type I cells in which IRF-7 could be induced. Finally, IFN-α, but not IFN-γ repressed endogenous Qp activity, which is consistent with the ability of IFN-α to induce IRF-7. Thus, IRF-7 may mediate repression of Qp by LMP-1. The induction of IRF-7 by LMP-1 may be relevant to the silencing of Qp in EBV type III latency.

Original languageEnglish (US)
Pages (from-to)1061-1068
Number of pages8
JournalJournal of virology
Volume74
Issue number3
DOIs
StatePublished - Jan 24 2000

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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