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Virol Res J 2017 Volume 1 Issue 3

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International Virology Conference

October 30-31, 2017 | Toronto, Canada

E

pstein-Barr virus (EBV) is a common herpesvirus that is

a causative factor in several types of lymphoma as well as

gastric and nasopharyngeal carcinomas. In EBV latent infection,

cells are immortalized as a result of expression of a small

subset of proteins that always includes EBNA1. In addition to

maintaining the EBV genomes, EBNA1 alters cells to promote

survival and proliferation in part by inducing the degradation of

promyelocyticleukemia(PML)tumoursuppressorproteins.PML

proteins and the nuclear bodies that they form have antiviral

properties and are important for several cellular processes

including apoptosis. We have shown that PML degradation by

EBNA1 involves direct interactions of EBNA1 with CK2 kinase

and the PML IV isoform, triggering PML phosphorylation

and degradation, which promotes the survival of gastric and

nasopharyngeal carcinoma cells. EBV can also switch to a lytic

infectious cycle which involves the expression of ~80 proteins,

and accumulating data suggests that lytic protein expression

contributes to EBV-induced cancers. However, the functions

of many of the lytic EBV proteins are poorly characterized or

completely unknown. To gain insight into EBV lytic proteins that

manipulate cellular pathways, we have screened a library of

EBV proteins for those that affect a variety of cellular processes

including the DNA damage response (DDR). Herpesviruses

typically inhibit some aspects of the DDR to limit downstream

consequences, including apoptosis. Our screen identified an

uncharacterized EBV tegument protein as an inhibitor of the

DDR. Further studies determined that the block in the DDR

was at the step of histone ubiquitylation and that the EBV

protein bound directly to histones. Furthermore, analysis

of transcriptome data from EBV-positive gastric carcinomas

showed that this EBV protein is expressed in these tumours.

Together our results suggest mechanisms by which both EBV

latent and lytic proteins contribute to oncogenesis.

Speaker Biography

Lori Frappier is a Professor of Molecular Genetics at the University of Toronto and

a Tier 1 Canada Research Chair in Molecular Virology. Her lab is known for their work

on understanding the structure, function and mechanisms of action of Epstein-Barr

virus proteins, including EBNA1, as well as of cellular targets of EBNA1, including

USP7. Their use of unbiased proteomics approaches has led to several discoveries of

viral-host interactions, novel functions for viral and cellular proteins and new

mechanisms of regulation of cellular pathways.

e:

lori.frappier@utoronto.ca

Lori Frappier

University of Toronto, Canada

Epstein-Barr virus manipulation of host responses