Epstein-Barr virus particles induce centrosome amplification and chromosomal instability

Anatoliy Shumilov; Ming Han Tsai; Yvonne T. Schlosser; Anne Sophie Kratz; Katharina Bernhardt; Susanne Fink; Tuba Mizani; Xiaochen Lin; Anna Jauch; Josef Mautner; Annette Kopp-Schneider; Regina Feederle; Ingrid Hoffmann; Henri Jacques Delecluse

doi:10.1038/ncomms14257

Epstein-Barr virus particles induce centrosome amplification and chromosomal instability

Anatoliy Shumilov, Ming Han Tsai, Yvonne T. Schlosser, Anne Sophie Kratz, Katharina Bernhardt, Susanne Fink, Tuba Mizani, Xiaochen Lin, Anna Jauch, Josef Mautner, Annette Kopp-Schneider, Regina Feederle, Ingrid Hoffmann, Henri Jacques Delecluse^*

^*Corresponding author for this work

Institute of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

71 Scopus citations

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.

Original language	English
Article number	14257
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14257
State	Published - 10 Feb 2017

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Shumilov, A., Tsai, M. H., Schlosser, Y. T., Kratz, A. S., Bernhardt, K., Fink, S., Mizani, T., Lin, X., Jauch, A., Mautner, J., Kopp-Schneider, A., Feederle, R., Hoffmann, I., & Delecluse, H. J. (2017). Epstein-Barr virus particles induce centrosome amplification and chromosomal instability. Nature Communications, 8, Article 14257. https://doi.org/10.1038/ncomms14257

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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.",

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AU - Shumilov, Anatoliy

AU - Tsai, Ming Han

AU - Schlosser, Yvonne T.

AU - Kratz, Anne Sophie

AU - Bernhardt, Katharina

AU - Fink, Susanne

AU - Mizani, Tuba

AU - Lin, Xiaochen

AU - Jauch, Anna

AU - Mautner, Josef

AU - Kopp-Schneider, Annette

AU - Feederle, Regina

AU - Hoffmann, Ingrid

AU - Delecluse, Henri Jacques

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N2 - 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.

AB - 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.

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SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 14257

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Epstein-Barr virus particles induce centrosome amplification and chromosomal instability

Abstract

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