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Interferon regulatory factor 7 is induced by Epstein-Barr virus latent membrane protein 1.
J Virol. 2000 Feb; 74(3):1061-8.JV

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 III 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-alpha, but not IFN-gamma, repressed endogenous Qp activity, which is consistent with the ability of IFN-alpha 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.

Authors+Show Affiliations

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA. luzhang@med.unc.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10627515

Citation

Zhang, L, and J S. Pagano. "Interferon Regulatory Factor 7 Is Induced By Epstein-Barr Virus Latent Membrane Protein 1." Journal of Virology, vol. 74, no. 3, 2000, pp. 1061-8.
Zhang L, Pagano JS. Interferon regulatory factor 7 is induced by Epstein-Barr virus latent membrane protein 1. J Virol. 2000;74(3):1061-8.
Zhang, L., & Pagano, J. S. (2000). Interferon regulatory factor 7 is induced by Epstein-Barr virus latent membrane protein 1. Journal of Virology, 74(3), 1061-8.
Zhang L, Pagano JS. Interferon Regulatory Factor 7 Is Induced By Epstein-Barr Virus Latent Membrane Protein 1. J Virol. 2000;74(3):1061-8. PubMed PMID: 10627515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interferon regulatory factor 7 is induced by Epstein-Barr virus latent membrane protein 1. AU - Zhang,L, AU - Pagano,J S, PY - 2000/1/11/pubmed PY - 2000/1/11/medline PY - 2000/1/11/entrez SP - 1061 EP - 8 JF - Journal of virology JO - J. Virol. VL - 74 IS - 3 N2 - 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 III 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-alpha, but not IFN-gamma, repressed endogenous Qp activity, which is consistent with the ability of IFN-alpha 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. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/10627515/Interferon_regulatory_factor_7_is_induced_by_Epstein_Barr_virus_latent_membrane_protein_1_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=10627515 DB - PRIME DP - Unbound Medicine ER -