Cell Reports
(Dec 2013)
Human Natural Killer Cells Prevent Infectious Mononucleosis Features by Targeting Lytic Epstein-Barr Virus Infection
Obinna Chijioke,
Anne Müller,
Regina Feederle,
Mario Henrique M. Barros,
Carsten Krieg,
Vanessa Emmel,
Emanuela Marcenaro,
Carol S. Leung,
Olga Antsiferova,
Vanessa Landtwing,
Walter Bossart,
Alessandro Moretta,
Rocio Hassan,
Onur Boyman,
Gerald Niedobitek,
Henri-Jacques Delecluse,
Riccarda Capaul,
Christian Münz
Affiliations
Obinna Chijioke
Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Anne Müller
Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Regina Feederle
DKFZ unit F100/INSERM unit U1074, 69120 Heidelberg, Germany
Mario Henrique M. Barros
Institute for Pathology, Unfallkrankenhaus Berlin, 12683 Berlin, Germany
Carsten Krieg
Laboratory of Applied Immunobiology, University of Zürich, 8006 Zürich, Switzerland
Vanessa Emmel
Bone Marrow Transplantation Center, Instituto Nacional de Cancer (INCA), 20231-130 Rio de Janeiro, Brazil
Emanuela Marcenaro
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16147 Genova, Italy
Carol S. Leung
Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Olga Antsiferova
Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Vanessa Landtwing
Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Walter Bossart
Institute of Medical Virology, University of Zürich, 8006 Zürich, Switzerland
Alessandro Moretta
Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16147 Genova, Italy
Rocio Hassan
Bone Marrow Transplantation Center, Instituto Nacional de Cancer (INCA), 20231-130 Rio de Janeiro, Brazil
Onur Boyman
Laboratory of Applied Immunobiology, University of Zürich, 8006 Zürich, Switzerland
Gerald Niedobitek
Institute for Pathology, Unfallkrankenhaus Berlin, 12683 Berlin, Germany
Henri-Jacques Delecluse
DKFZ unit F100/INSERM unit U1074, 69120 Heidelberg, Germany
Riccarda Capaul
Institute of Medical Virology, University of Zürich, 8006 Zürich, Switzerland
Christian Münz
Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
DOI
https://doi.org/10.1016/j.celrep.2013.11.041
Journal volume & issue
Vol. 5,
no. 6
Abstract
Read online
Primary infection with the human oncogenic Epstein-Barr virus (EBV) can result in infectious mononucleosis (IM), a self-limiting disease caused by massive lymphocyte expansion that predisposes for the development of distinct EBV-associated lymphomas. Why some individuals experience this symptomatic primary EBV infection, whereas the majority acquires the virus asymptomatically, remains unclear. Using a mouse model with reconstituted human immune system components, we show that depletion of human natural killer (NK) cells enhances IM symptoms and promotes EBV-associated tumorigenesis mainly because of a loss of immune control over lytic EBV infection. These data suggest that failure of innate immune control by human NK cells augments symptomatic lytic EBV infection, which drives lymphocyte expansion and predisposes for EBV-associated malignancies.
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