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Albanese, M. ; Tagawa, T. ; Bouvet, M. ; Maliqi, L. ; Lutter, D. ; Hoser, J.D.S. ; Hastreiter, M. ; Hayes, M.* ; Sugden, B.* ; Martin, L. ; Moosmann, A. ; Hammerschmidt, W.

Epstein-Barr virus microRNAs reduce immune surveillance by virus-specific CD8+ T cells.

Proc. Natl. Acad. Sci. U.S.A. 113, E6467-E6475 (2016)
Publ. Version/Full Text Research data DOI PMC
Infection with Epstein-Barr virus (EBV) affects most humans worldwide and persists life-long in the presence of robust virus-specific T-cell responses. In both immunocompromised and some immunocompetent people, EBV causes several cancers and lymphoproliferative diseases. EBV transforms B cells in vitro and encodes at least 44 microRNAs (miRNAs), most of which are expressed in EBV-transformed B cells, but their functions are largely unknown. Recently, we showed that EBV miRNAs inhibit CD4(+) T-cell responses to infected B cells by targeting IL-12, MHC class II, and lysosomal proteases. Here we investigated whether EBV miRNAs also counteract surveillance by CD8(+) T cells. We have found that EBV miRNAs strongly inhibit recognition and killing of infected B cells by EBV-specific CD8(+) T cells through multiple mechanisms. EBV miRNAs directly target the peptide transporter subunit TAP2 and reduce levels of the TAP1 subunit, MHC class I molecules, and EBNA1, a protein expressed in most forms of EBV latency and a target of EBV-specific CD8(+) T cells. Moreover, miRNA-mediated down-regulation of the cytokine IL-12 decreases the recognition of infected cells by EBV-specific CD8(+) T cells. Thus, EBV miRNAs use multiple, distinct pathways, allowing the virus to evade surveillance not only by CD4(+) but also by antiviral CD8(+) T cells.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cd8 T Cells ; Adaptive Immunity ; Herpesvirus ; Immune Evasion ; Microrna; Lymphoproliferative Disease; B-cells; Antigen Presentation; Encoded Micrornas; Cycle Antigens; Host Shutoff; Lytic Phase; Ebv; Lymphocytes; Responses
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 113, Issue: 42, Pages: E6467-E6475 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Publishing Place Washington
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Institute of Diabetes and Obesity (IDO)
Institute of Bioinformatics and Systems Biology (IBIS)