title: Epstein-Barr virus particles induce centrosome amplification and chromosomal instability.
abstract: Infections with Epstein-Barr virus (EBV) are associated with cancer development, and EBV lytic replication (the process that generates virus progeny) is a strong risk factor for some cancer types. Here we report that EBV infection of B-lymphocytes (in vitro and in a mouse model) leads to an increased rate of centrosome amplification, associated with chromosomal instability. This effect can be reproduced with virus-like particles devoid of EBV DNA, but not with defective virus-like particles that cannot infect host cells. Viral protein BNRF1 induces centrosome amplification, and BNRF1-deficient viruses largely lose this property. These findings identify a new mechanism by which EBV particles can induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for development of tumours that do not necessarily carry the viral genome.
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F100, 69120 Heidelberg, Germany.|Inserm unit U1074, DKFZ, 69120 Heidelberg, Germany.|German Centre for Infection Research (DZIF), 69120 Heidelberg, Germany.
authors.forename: Anatoliy
authors.initials: A
authors.lastname: Shumilov
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F100, 69120 Heidelberg, Germany.|Inserm unit U1074, DKFZ, 69120 Heidelberg, Germany.|German Centre for Infection Research (DZIF), 69120 Heidelberg, Germany.
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F045, 69120 Heidelberg, Germany.
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: Schlosser
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F045, 69120 Heidelberg, Germany.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Kratz
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F100, 69120 Heidelberg, Germany.|Inserm unit U1074, DKFZ, 69120 Heidelberg, Germany.|German Centre for Infection Research (DZIF), 69120 Heidelberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Bernhardt
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F100, 69120 Heidelberg, Germany.|Inserm unit U1074, DKFZ, 69120 Heidelberg, Germany.|German Centre for Infection Research (DZIF), 69120 Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fink
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F100, 69120 Heidelberg, Germany.|Inserm unit U1074, DKFZ, 69120 Heidelberg, Germany.|German Centre for Infection Research (DZIF), 69120 Heidelberg, Germany.
authors.forename: Tuba
authors.initials: T
authors.lastname: Mizani
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F100, 69120 Heidelberg, Germany.|Inserm unit U1074, DKFZ, 69120 Heidelberg, Germany.|German Centre for Infection Research (DZIF), 69120 Heidelberg, Germany.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Lin
authors.affiliation: Institute of Human Genetics University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.affiliation: Helmholtz Zentrum München, Research Unit Gene Vectors, 81377 Munich, Germany.|Children's Hospital Technische Universität München, 80804 Munich, Germany.|German Center for Infection Research (DZIF), 81377 Munich, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Mautner
authors.affiliation: German Cancer Research Centre (DKFZ), Unit C060, 69120 Heidelberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Kopp-Schneider
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F100, 69120 Heidelberg, Germany.|Inserm unit U1074, DKFZ, 69120 Heidelberg, Germany.|Helmholtz Zentrum München, German Research Center for Environmental Health, Institute for Diabetes and Obesity, Core Facility Monoclonal Antibodies, 81377 Munich, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Feederle
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F045, 69120 Heidelberg, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hoffmann
authors.affiliation: German Cancer Research Centre (DKFZ), Unit F100, 69120 Heidelberg, Germany.|Inserm unit U1074, DKFZ, 69120 Heidelberg, Germany.|German Centre for Infection Research (DZIF), 69120 Heidelberg, Germany.
authors.forename: Henri-Jacques
authors.initials: HJ
authors.lastname: Delecluse
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D018385:Centrosome / Q000378:metabolism / Q000821:virology*; D043171:Chromosomal Instability; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000821:virology*; D057809:HEK293 Cells; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000502:physiology
chemical_list: C062724:P140 protein, Epstein-barr virus; D014759:Viral Envelope Proteins