EBV particles induce chromosome instability

Chih-Ying Lee, PhD

Infections with the 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. We have recently reported that EBV infection of B-lymphocytes in vitro and in a mouse model leads to an increased rate of centrosome amplification (Figure 1), associated with chromosomal instability (Figure 2). Importantly, 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 because they lack a glycoprotein involved in target cell entry.

We could first identify the viral tegument protein BNRF1 as an inducer of centrosome amplification though over-duplication of the centrosome machinery. EBV mutants that lack BNRF1 have lost this property but it can be restored by reintroduction of the BNRF1 protein into the virus particle. Importantly, BNRF1 localizes to the centrosome compartment in transfected cells. This identifies a new mechanism by which EBV particles can induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for development of tumors that do not necessarily carry the viral genome.

Current projects look at the contribution of other EBV proteins to the development of genetic instability and how they interact with the cell machinery to cause these abnormalities.