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Tagawa, T. ; Albanese, M. ; Bouvet, M. ; Moosmann, A. ; Mautner, J. ; Heissmeyer, V. ; Zielinski, C.* ; Lutter, D. ; Hoser, J.D.S. ; Hastreiter, M. ; Hayes, M.* ; Sugden, B.* ; Hammerschmidt, W.

Epstein-Barr viral miRNAs inhibit antiviral CD4+ T cell responses targeting IL-12 and peptide processing.

J. Exp. Med. 213, 2065-2080 (2016)
Publ. Version/Full Text Research data DOI PMC
Creative Commons Lizenzvertrag
Open Access Green as soon as Postprint is submitted to ZB.
Epstein-Barr virus (EBV) is a tumor virus that establishes lifelong infection in most of humanity, despite eliciting strong and stable virus-specific immune responses. EBV encodes at least 44 miRNAs, most of them with unknown function. Here, we show that multiple EBV miRNAs modulate immune recognition of recently infected primary B cells, EBV's natural target cells. EBV miRNAs collectively and specifically suppress release of proinflammatory cytokines such as IL-12, repress differentiation of naive CD4(+) T cells to Th1 cells, interfere with peptide processing and presentation on HLA class II, and thus reduce activation of cytotoxic EBV-specific CD4(+) effector T cells and killing of infected B cells. Our findings identify a previously unknown viral strategy of immune evasion. By rapidly expressing multiple miRNAs, which are themselves nonimmunogenic, EBV counteracts recognition by CD4(+) T cells and establishes a program of reduced immunogenicity in recently infected B cells, allowing the virus to express viral proteins required for establishment of life-long infection.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Human B-cells; Virus Infection; Immune Evasion; Lymphoproliferative Disorders; Micrornas Target; Ebv; Recognition; Lymphocytes; Herpesvirus; Expression
ISSN (print) / ISBN 0022-1007
e-ISSN 1540-9538
Journal Journal of Experimental Medicine
Quellenangaben Volume: 213, Issue: 10, Pages: 2065-2080 Article Number: , Supplement: ,
Publisher Rockefeller University Press
Publishing Place New York
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Abteilung für Molekulare Immunregulation (AMIR)
Institute of Diabetes and Obesity (IDO)
Institute of Bioinformatics and Systems Biology (IBIS)