title: Human natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein-Barr virus infection.
abstract: 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.
authors.affiliation: Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Obinna
authors.initials: O
authors.lastname: Chijioke
authors.affiliation: Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Müller
authors.affiliation: DKFZ unit F100/INSERM unit U1074, 69120 Heidelberg, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Feederle
authors.affiliation: Institute for Pathology, Unfallkrankenhaus Berlin, 12683 Berlin, Germany.
authors.forename: Mario Henrique M
authors.initials: MH
authors.lastname: Barros
authors.affiliation: Laboratory of Applied Immunobiology, University of Zürich, 8006 Zürich, Switzerland.
authors.forename: Carsten
authors.initials: C
authors.lastname: Krieg
authors.affiliation: Bone Marrow Transplantation Center, Instituto Nacional de Cancer (INCA), 20231-130 Rio de Janeiro, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Emmel
authors.affiliation: Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16147 Genova, Italy; Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, 16147 Genova, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.affiliation: Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Carol S
authors.initials: CS
authors.lastname: Leung
authors.affiliation: Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Olga
authors.initials: O
authors.lastname: Antsiferova
authors.affiliation: Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Landtwing
authors.affiliation: Institute of Medical Virology, University of Zürich, 8006 Zürich, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Bossart
authors.affiliation: Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16147 Genova, Italy; Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, 16147 Genova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Bone Marrow Transplantation Center, Instituto Nacional de Cancer (INCA), 20231-130 Rio de Janeiro, Brazil.
authors.forename: Rocio
authors.initials: R
authors.lastname: Hassan
authors.affiliation: Laboratory of Applied Immunobiology, University of Zürich, 8006 Zürich, Switzerland.
authors.forename: Onur
authors.initials: O
authors.lastname: Boyman
authors.affiliation: Institute for Pathology, Unfallkrankenhaus Berlin, 12683 Berlin, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Niedobitek
authors.affiliation: DKFZ unit F100/INSERM unit U1074, 69120 Heidelberg, Germany.
authors.forename: Henri-Jacques
authors.initials: HJ
authors.lastname: Delecluse
authors.affiliation: Institute of Medical Virology, University of Zürich, 8006 Zürich, Switzerland.
authors.forename: Riccarda
authors.initials: R
authors.lastname: Capaul
authors.affiliation: Department of Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland. Electronic address: christian.muenz@uzh.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D007244:Infectious Mononucleosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015534:Trans-Activators / Q000276:immunology
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D015534:Trans-Activators