Epstein-Barr virus microRNAs reduce immune surveillance by virus-specific CD8+ T cells
| Autor: | Takanobu Tagawa, Liridona Maliqi, Jonathan Hoser, Larissa K. Martin, Maximilian Hastreiter, Manuel Albanese, Mickaël Bouvet, Mitch Hayes, Andreas Moosmann, Dominik Lutter, Wolfgang Hammerschmidt, Bill Sugden |
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| Jazyk: | němčina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytotoxicity Immunologic Gene Expression Regulation Viral Epstein-Barr Virus Infections Herpesvirus 4 Human Cd8 T Cells Adaptive Immunity Herpesvirus Immune Evasion Microrna Cell Survival medicine.medical_treatment Epitopes T-Lymphocyte CD8-Positive T-Lymphocytes medicine.disease_cause Virus Cell Line 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases MHC class I medicine Cytotoxic T cell Humans Receptors Cytokine Immunologic Surveillance MHC class II Antigen Presentation B-Lymphocytes Multidisciplinary biology Histocompatibility Antigens Class I Acquired immune system Epstein–Barr virus Virology MicroRNAs 030104 developmental biology Cytokine PNAS Plus biology.protein Cytokines RNA Viral CD8 030215 immunology |
| Zdroj: | Proc. Natl. Acad. Sci. U.S.A. 113, E6467-E6475 (2016) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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