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

Proc. Natl. Acad. Sci. U.S.A. 113, E6467-E6475 (2016)
Verlagsversion Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Quellenangaben Band: 113, Heft: 42, Seiten: E6467-E6475 Artikelnummer: , Supplement: ,
Verlag National Academy of Sciences
Verlagsort Washington
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed