3 / 3
Page 11
Virol Res J 2017 Volume 1 Issue 3
allied
academies
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.caLori Frappier
University of Toronto, Canada
Epstein-Barr virus manipulation of host responses