Epstein-Barr virus particles induce centrosome amplification and chromosomal instability.

Fiche publication


Date publication

février 2017

Journal

Nature communications

Auteurs

Membres identifiés du Cancéropôle Est :
Pr DELECLUSE Henri-Jacques


Tous les auteurs :
Shumilov A, Tsai MH, Schlosser YT, Kratz AS, Bernhardt K, Fink S, Mizani T, Lin X, Jauch A, Mautner J, Kopp-Schneider A, Feederle R, Hoffmann I, Delecluse HJ

Résumé

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.

Mots clés

Animals, B-Lymphocytes, metabolism, Cell Line, Cell Line, Tumor, Cell Transformation, Neoplastic, Centrosome, metabolism, Chromosomal Instability, Epstein-Barr Virus Infections, genetics, HEK293 Cells, HeLa Cells, Herpesvirus 4, Human, genetics, Humans, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Viral Envelope Proteins, genetics, Virion, genetics

Référence

Nat Commun. 2017 Feb;8:14257