EBV MicroRNA BART16 Suppresses Type I IFN Signaling.

Abstract

Type I IFNs play critical roles in orchestrating the antiviral defense by inducing direct antiviral activities and shaping the adaptive immune response. Viruses have evolved numerous strategies to specifically interfere with IFN production or its downstream mediators, thereby allowing successful infection of the host to occur. The prototypic human gammaherpesvirus EBV, which is associated with infectious mononucleosis and malignant tumors, harbors many immune-evasion proteins that manipulate the adaptive and innate immune systems. In addition to proteins, the virus encodes >40 mature microRNAs for which the functions remain largely unknown. In this article, we identify EBV-encoded miR-BART16 as a novel viral immune-evasion factor that interferes with the type I IFN signaling pathway. miR-BART16 directly targets CREB-binding protein, a key transcriptional coactivator in IFN signaling, thereby inducing CREB-binding protein downregulation in EBV-transformed B cells and gastric carcinoma cells. miR-BART16 abrogates the production of IFN-stimulated genes in response to IFN-α stimulation and it inhibits the antiproliferative effect of IFN-α on latently infected BL cells. By obstructing the type I IFN-induced antiviral response, miR-BART16 provides a means to facilitate the establishment of latent EBV infection and enhance viral replication.

• Authors: Marjolein J G Hooykaas, Michiel van Gent, Jasper A Soppe, Elisabeth Kruse, Ingrid G J Boer, Dik van Leenen, Marian J A Groot Koerkamp, Frank C P Holstege, Maaike E Ressing, Emmanuel J H J Wiertz, Robert Jan Lebbink
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 198 Issue 10 Pg. 4062-4073 (05 15 2017) ISSN: 1550-6606 [Electronic] United States
• PMID: 28416598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 by The American Association of Immunologists, Inc.

Chemical References

• Interferon Type I
• MicroRNAs
• RNA, Viral
• CREB-Binding Protein

Topics

• CREB-Binding Protein (metabolism)
• Cell Line
• Herpesvirus 4, Human (genetics, immunology)
• Host-Pathogen Interactions
• Humans
• Immune Evasion
• Immunity, Innate
• Interferon Type I (immunology, metabolism)
• MicroRNAs (genetics, metabolism)
• RNA, Viral (genetics, metabolism)
• Signal Transduction
• Virus Replication