MicroRNAs of Epstein-Barr Virus Attenuate T-Cell-Mediated Immune Control
| العنوان: | MicroRNAs of Epstein-Barr Virus Attenuate T-Cell-Mediated Immune Control |
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| المؤلفون: | Andrea Zbinden, Julia Rühl, Wolfgang Hammerschmidt, Anita Murer, Christian Münz, Riccarda Capaul, Obinna Chijioke |
| المساهمون: | University of Zurich, Chijioke, Obinna |
| المصدر: | mBio mBio 10:01941-18 (2019) mBio, Vol 10, Iss 1 (2019) mBio, Vol 10, Iss 1, p e01941-18 (2019) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 10028 Institute of Medical Virology, Epstein-Barr Virus Infections, Herpesvirus 4, Human, T-Lymphocytes, medicine.disease_cause, 10263 Institute of Experimental Immunology, Mice, 0302 clinical medicine, hemic and lymphatic diseases, Cytotoxic T cell, 0303 health sciences, B-Lymphocytes, 2404 Microbiology, Viral Load, QR1-502, 3. Good health, humanized mice, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Host-Pathogen Interactions, RNA, Viral, Erratum, Viral load, Research Article, T cell, Lymphoproliferative disorders, lymphoma, 610 Medicine & health, Mice, Transgenic, Biology, Microbiology, Virus, Host-Microbe Biology, 03 medical and health sciences, Epstein-barr Virus, Cytotoxic T Cells, Humanized Mice, Immune Escape, Lymphoma, Mirna, Immune system, Virology, medicine, Epstein-Barr virus, Animals, Humans, miRNA, 030304 developmental biology, Immune Evasion, cytotoxic T cells, immune escape, medicine.disease, Epstein–Barr virus, Disease Models, Animal, MicroRNAs, 2406 Virology, 570 Life sciences, biology, CD8, Gene Deletion |
| الوصف: | Epstein-Barr virus (EBV) infects the majority of the human population and usually persists asymptomatically within its host. Nevertheless, EBV is the causative agent for infectious mononucleosis (IM) and for lymphoproliferative disorders, including Burkitt and Hodgkin lymphomas. The immune system of the infected host is thought to prevent tumor formation in healthy virus carriers. EBV was one of the first viruses described to express miRNAs, and many host and viral targets were identified for these in vitro. However, their role during EBV infection in vivo remained unclear. This work is the first to describe that EBV miRNAs mainly increase viremia and virus-associated lymphomas through dampening antigen recognition by adaptive immune responses in mice with reconstituted immune responses. Currently, there is no prophylactic or therapeutic treatment to restrict IM or EBV-associated malignancies; thus, targeting EBV miRNAs could promote immune responses and limit EBV-associated pathologies. The human persistent and oncogenic Epstein-Barr virus (EBV) was one of the first viruses that were described to express viral microRNAs (miRNAs). These have been proposed to modulate many host and viral functions, but their predominant role in vivo has remained unclear. We compared recombinant EBVs expressing or lacking miRNAs during in vivo infection of mice with reconstituted human immune system components and found that miRNA-deficient EBV replicates to lower viral titers with decreased frequencies of proliferating EBV-infected B cells. In response, activated cytotoxic EBV-specific T cells expand to lower frequencies than during infection with miRNA-expressing EBV. However, when we depleted CD8+ T cells the miRNA-deficient virus reached similar viral loads as wild-type EBV, increasing by more than 200-fold in the spleens of infected animals. Furthermore, CD8+ T cell depletion resulted in lymphoma formation in the majority of animals after miRNA-deficient EBV infection, while no tumors emerged when CD8+ T cells were present. Thus, miRNAs mainly serve the purpose of immune evasion from T cells in vivo and could become a therapeutic target to render EBV-associated malignancies more immunogenic. |
| وصف الملف: | mBio-2019-Murer-e01941-18.full.pdf - application/pdf; application/pdf |
| تدمد: | 2150-7511 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::391e643fe0d44565e9a3671522f776dbTest https://pubmed.ncbi.nlm.nih.gov/31337725Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....391e643fe0d44565e9a3671522f776db |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21507511 |
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