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MicroRNAs of Epstein-Barr Virus Attenuate T-Cell-Mediated Immune Control
- Source :
- mBio, mBio 10:01941-18 (2019), mBio, Vol 10, Iss 1 (2019), mBio, Vol 10, Iss 1, p e01941-18 (2019)
- Publication Year :
- 2019
-
Abstract
- 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.<br />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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 21507511
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- mBio
- Accession number :
- edsair.doi.dedup.....391e643fe0d44565e9a3671522f776db