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


Autoři: Susanne Delecluse aff001;  Jiyang Yu aff001;  Katharina Bernhardt aff001;  Janina Haar aff001;  Remy Poirey aff001;  Ming-Han Tsai aff001;  Rama Kiblawi aff001;  Annette Kopp-Schneider aff005;  Paul Schnitzler aff006;  Martin Zeier aff004;  Peter Dreger aff007;  Patrick Wuchter aff007;  Olcay Cem Bulut aff009;  Uta Behrends aff003;  Henri-Jacques Delecluse aff001
Působiště autorů: German Cancer Research Centre (DKFZ) Unit F100, Heidelberg, Germany aff001;  Institut National de la Santé et de la Recherche Médicale (INSERM) Unit U1074, Heidelberg, Germany aff002;  German Centre for Infection Research (DZIF), Braunschweig, Germany aff003;  Nierenzentrum Heidelberg, Heidelberg, Germany aff004;  German Cancer Research Centre (DKFZ), Unit C060, Heidelberg, Germany aff005;  Center for Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany aff006;  Department of Medicine V, University of Heidelberg, Heidelberg, Germany aff007;  Institute of Transfusion Medicine and Immunology, German Red Cross Blood Donor Service Baden-Württemberg–Hessen, Medical Faculty Mannheim, Heidelberg University, Germany aff008;  Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany aff009;  Children’s Hospital Klinikum Rechts der Isar, Technische Universitaet Muenchen, Munich, Germany aff010
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222847

Souhrn

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.

Klíčová slova:

Apoptosis – B cells – Epstein-Barr virus – MicroRNAs – Multiple alignment calculation – Protein expression – Sequence alignment – Stem cell transplantation


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