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

doi:10.1016/j.celrep.2013.11.041

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

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182 Scopus citations

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.

Original language	English
Pages (from-to)	1489-1498
Number of pages	10
Journal	Cell Reports
Volume	5
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2013.11.041
State	Published - 26 Dec 2013
Externally published	Yes

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Chijioke, O., Müller, A., Feederle, R., Barros, M. H. M., Krieg, C., Emmel, V., Marcenaro, E., Leung, C. S., Antsiferova, O., Landtwing, V., Bossart, W., Moretta, A., Hassan, R., Boyman, O., Niedobitek, G., Delecluse, H. J., Capaul, R., & Münz, C. (2013). Human natural killer cells prevent infectious mononucleosis features by targeting lytic epstein-barr virus infection. Cell Reports, 5(6), 1489-1498. https://doi.org/10.1016/j.celrep.2013.11.041

@article{09c8c4e5e21c44f7938fa39b2a8abfb1,

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.",

author = "Obinna Chijioke and Anne M{\"u}ller and Regina Feederle and Barros, {Mario Henrique M.} and Carsten Krieg and Vanessa Emmel and Emanuela Marcenaro and Leung, {Carol S.} and Olga Antsiferova and Vanessa Landtwing and Walter Bossart and Alessandro Moretta and Rocio Hassan and Onur Boyman and Gerald Niedobitek and Delecluse, {Henri Jacques} and Riccarda Capaul and Christian M{\"u}nz",

note = "Funding Information: We are grateful to Drs. Maike Ressing, Emmanuel Wiertz, and Martin Rowe for providing the AKBM cells and to Silvia Behnke of Sophistolabs for the histology in Figure S4 . This work was supported by the National Cancer Institute (R01CA108609), the Sassella Foundation (10/02, 11/02, and 12/02), the Cancer Research Switzerland (KFS-02652-08-2010), the Association for International Cancer Research (11-0516), KFSP MS and KFSP HLD of the University of Z{\"u}rich, the Vontobel Foundation, the Baugarten Foundation, the EMDO Foundation, the Sobek Foundation, the Foundation Acteria, Novartis, and the Swiss National Science Foundation (310030_143979 and CRSII3_136241) to C.M. R.H. is a fellow of the CNPq/INCT (Brazil; grants CNPq 481294/2009-0, 573806/2008-0, and FAPERJ - E-26/110.432/2010). M.H.MB. is supported by the Alexander von Humboldt Foundation. O.C. is the recipient of a postdoctoral fellowship of the Deutsche Forschungsgemeinschaft (CH 723/2-1). ",

year = "2013",

month = dec,

day = "26",

doi = "10.1016/j.celrep.2013.11.041",

language = "English",

volume = "5",

pages = "1489--1498",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "6",

}

Chijioke, O, Müller, A, Feederle, R, Barros, MHM, Krieg, C, Emmel, V, Marcenaro, E, Leung, CS, Antsiferova, O, Landtwing, V, Bossart, W, Moretta, A, Hassan, R, Boyman, O, Niedobitek, G, Delecluse, HJ, Capaul, R & Münz, C 2013, 'Human natural killer cells prevent infectious mononucleosis features by targeting lytic epstein-barr virus infection', Cell Reports, vol. 5, no. 6, pp. 1489-1498. https://doi.org/10.1016/j.celrep.2013.11.041

TY - JOUR

T1 - Human natural killer cells prevent infectious mononucleosis features by targeting lytic epstein-barr virus infection

AU - Chijioke, Obinna

AU - Müller, Anne

AU - Feederle, Regina

AU - Barros, Mario Henrique M.

AU - Krieg, Carsten

AU - Emmel, Vanessa

AU - Marcenaro, Emanuela

AU - Leung, Carol S.

AU - Antsiferova, Olga

AU - Landtwing, Vanessa

AU - Bossart, Walter

AU - Moretta, Alessandro

AU - Hassan, Rocio

AU - Boyman, Onur

AU - Niedobitek, Gerald

AU - Delecluse, Henri Jacques

AU - Capaul, Riccarda

AU - Münz, Christian

N1 - Funding Information: We are grateful to Drs. Maike Ressing, Emmanuel Wiertz, and Martin Rowe for providing the AKBM cells and to Silvia Behnke of Sophistolabs for the histology in Figure S4 . This work was supported by the National Cancer Institute (R01CA108609), the Sassella Foundation (10/02, 11/02, and 12/02), the Cancer Research Switzerland (KFS-02652-08-2010), the Association for International Cancer Research (11-0516), KFSP MS and KFSP HLD of the University of Zürich, the Vontobel Foundation, the Baugarten Foundation, the EMDO Foundation, the Sobek Foundation, the Foundation Acteria, Novartis, and the Swiss National Science Foundation (310030_143979 and CRSII3_136241) to C.M. R.H. is a fellow of the CNPq/INCT (Brazil; grants CNPq 481294/2009-0, 573806/2008-0, and FAPERJ - E-26/110.432/2010). M.H.MB. is supported by the Alexander von Humboldt Foundation. O.C. is the recipient of a postdoctoral fellowship of the Deutsche Forschungsgemeinschaft (CH 723/2-1).

PY - 2013/12/26

Y1 - 2013/12/26

N2 - 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.

AB - 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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U2 - 10.1016/j.celrep.2013.11.041

DO - 10.1016/j.celrep.2013.11.041

M3 - Article

C2 - 24360958

AN - SCOPUS:84890973428

SN - 2211-1247

VL - 5

SP - 1489

EP - 1498

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -

Human natural killer cells prevent infectious mononucleosis features by targeting lytic epstein-barr virus infection

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