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Spontaneous lymphoblastoid cell lines from patients with Epstein-Barr virus infection show highly variable proliferation characteristics that correlate with the expression levels of viral microRNAs

Authors :
Patrick Wuchter
Jiyang Yu
Janina Haar
Paul Schnitzler
Ming Han Tsai
Martin Zeier
Katharina Bernhardt
Remy Poirey
Olcay Cem Bulut
Rama Kiblawi
Susanne Delecluse
Annette Kopp-Schneider
Henri Jacques Delecluse
Uta Behrends
Peter Dreger
Source :
PLoS ONE, PLoS ONE, Vol 14, Iss 9, p e0222847 (2019)
Publication Year :
2019

Abstract

The Epstein-Barr virus (EBV) induces B-cell proliferation with high efficiency through expression of latent proteins and microRNAs. This process takes place in vivo soon after infection, presumably to expand the virus reservoir, but can also induce pathologies, e.g. an infectious mononucleosis (IM) syndrome after primary infection or a B-cell lymphoproliferation in immunosuppressed individuals. In this paper, we investigated the growth characteristics of EBV-infected B-cells isolated from transplant recipients or patients with IM. We found that these cells grew and withstood apoptosis at highly variable rates, suggesting that the expansion rate of the infected B-cells widely varies between individuals, thereby influencing the size of the B-cell reservoir and the ability to form tumors in infected individuals. All viruses investigated were type 1 and genetically close to western strains. EBV-infected B-cells expressed the transforming EBV latent genes and microRNAs (miRNAs) at variable levels. We found that the B-cell growth rates positively correlated with the BHRF1 miRNA levels. Comparative studies showed that infected B-cells derived from transplant recipients with iEBVL on average expressed higher levels of EBV miR-BHRF1 miRNAs and grew more rapidly than B-cells from IM patients, suggesting infection by more transforming viruses. Altogether, these findings suggest that EBV infection has a highly variable impact on the B-cell compartment that probably reflects the genetic diversity of both the virus and the host. It also demonstrates the unexpected finding that B-cells from different individuals can grow at different speed under the influence of the same virus infection.

Subjects

Subjects :
0301 basic medicine
Male
Herpesvirus 4, Human
B Cells
Mononucleosis
Genes, Viral
Cell Transplantation
Protein Expression
Apoptosis
Biochemistry
White Blood Cells
Database and Informatics Methods
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
Blood and Lymphatic System Procedures
Pathology and laboratory medicine
Cell Line, Transformed
Regulation of gene expression
B-Lymphocytes
Multidisciplinary
Cell Death
Hematopoietic Stem Cell Transplantation
Middle Aged
Medical microbiology
Nucleic acids
Cell Processes
030220 oncology & carcinogenesis
Host-Pathogen Interactions
Viruses
Medicine
Female
Cellular Types
Pathogens
Sequence Analysis
Research Article
Adult
Gene Expression Regulation, Viral
Herpesviruses
Multiple Alignment Calculation
Bioinformatics
Science
Immune Cells
Primary Cell Culture
Immunology
Surgical and Invasive Medical Procedures
Biology
Research and Analysis Methods
Microbiology
Virus
03 medical and health sciences
Immunocompromised Host
Viral Proteins
microRNA
Computational Techniques
medicine
Genetics
Gene Expression and Vector Techniques
Humans
Epstein-Barr virus
Infectious Mononucleosis
Non-coding RNA
Antibody-Producing Cells
Molecular Biology Techniques
Gene
Epstein–Barr virus infection
Molecular Biology
Aged
Cell Proliferation
Natural antisense transcripts
Transplantation
Molecular Biology Assays and Analysis Techniques
Blood Cells
Biology and life sciences
Organisms
Viral pathogens
Cell Biology
medicine.disease
Virology
Kidney Transplantation
Split-Decomposition Method
Gene regulation
Microbial pathogens
MicroRNAs
030104 developmental biology
Cell culture
RNA
Gene expression
DNA viruses
Sequence Alignment
Stem Cell Transplantation

Details

ISSN :
19326203
Volume :
14
Issue :
9
Database :
OpenAIRE
Journal :
PloS one
Accession number :
edsair.doi.dedup.....e03d4db5e9a3d29128c3f9bc55a2b5de