NDLI: Role of IRF4 in IFN-stimulated gene induction and maintenance of Kaposi sarcoma-associated herpesvirus latency in primary effusion lymphoma cells.

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Role of IRF4 in IFN-stimulated gene induction and maintenance of Kaposi sarcoma-associated herpesvirus latency in primary effusion lymphoma cells.

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Role of IRF4 in IFN-stimulated gene induction and maintenance of Kaposi sarcoma-associated herpesvirus latency in primary effusion lymphoma cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sarkar, Saumendra N. Moore, Patrick S. Forero, Adriana
Description	Country affiliation: United States Author Affiliation: Forero A ( Cancer Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.)
Abstract	IFN regulatory factor (IRF) 4 is a hematopoietic cell-specific transcription factor that regulates the maturation and differentiation of immune cells. Using an inducible expression system, we found that IRF4 directly induced a specific subset of IFN-stimulated genes (ISGs) in a type I IFN-independent manner in both epithelial and B cell lines. Moreover, Kaposi sarcoma-associated herpesvirus (KSHV)-encoded viral FLICE inhibitory protein (vFLIP) enhances IRF4-mediated gene induction. Coexpression of IRF4 with vFLIP significantly increased ISG60 (IFIT3) and Cig5 (RSAD2) transcription that was dependent on the ability of vFLIP to activate NF-κB. A vFLIP mutant (A57L) defective in NF-κB activation failed to enhance IRF4-mediated ISG induction. Thus, we provide a physiologically relevant mechanism by which viral protein-mediated NF-κB activation modulates specific ISG induction by IRF4. In contrast, IRF4 also acted as a negative regulator of KSHV replication and transcription activator expression after induction of KSHV lytic reactivation in KSHV-positive primary effusion lymphoma cells. Taken together, these results suggest a dual role for IRF4 in regulating ISG induction and KSHV lytic reactivation in primary effusion lymphoma cells.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1202514
Journal	The Journal of Immunology
Issue Number	3
Volume Number	191
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Herpesvirus 8, Human Metabolism Interferon Regulatory Factors Intracellular Signaling Peptides And Proteins Genetics Proteins Casp8 And Fadd-like Apoptosis Regulating Protein Cell Line, Transformed Enzyme Activation Gene Expression Gene Expression Regulation Hek293 Cells Interferon Type I Lymphoma Virology Mutation Nf-kappa B Transcription, Genetic Transcriptional Activation Virus Latency Virus Replication Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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