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.

Abstract

Infection with Epstein–Barr virus (EBV) is associated with increased risk of cancer development. Here the authors show that EBV particles, and more specifically the viral protein BNRF1, induce centrosome amplification and chromosomal instability in host cells in the absence of chronic infection.