EBV Conference 2008 Guangzhou - Baylor College of Medicine

132 (RegID: 1230; 1231)
Stephen Murphy
Institution: CRUK Institute for Cancer Studies, University of Birmingham
e-mail: sfm694@bham.ac.uk
LMP2A MODULATES SIGNALLING FROM TOLL-LIKE RECEPTOR (TLR)-3 AND TLR-4 IN
HUMAN EPITHELIAL CELLS
S.F.Murphy, K.M Shah, C.W.Dawson and L.S.Young
Cancer Research (UK) Institute for Cancer Studies, School of Cancer Sciences, University of Birmingham,
Birmingham B15 2TT, UK
Posterabstract:
The EBV-encoded latent membrane protein, LMP2A, although not essential for viral transformation, plays
a key role in promoting cell survival and viral latency. Although frequently expressed in EBV-associated
carcinomas, the exact role that LMP2A plays in the maintenance of the transformed state remains to be
elucidated. Previous studies from our group have uncovered a novel role for LMP2A and LMP2B in
epithelial cells, namely, an ability to modulate signalling from type I and type II interferon receptors.
These studies have now been extended to examine the effects of LMP2A and LMP2B on activity of the
Toll-Like Receptor (TLR) family, focusing on those involved in viral immune responses (TLR 3, 4, 7 and
9). Both immunofluorescence staining and flow cytometery have established that TLR expression is
significantly reduced in LMP2A but not in LMP2B-expressing cells. Furthermore, when stimulated with
polyI:C or LPS, agonists which stimulate TLR3 and TLR4 respectively, LMP2A-expressing cells
appeared almost refractory to agonist stimulation as assessed by interferon-b promoter luciferase reporter
activity. Although LMP2B failed to attenuate TLR-mediated activation of IFN-b reporter constructs, both
LMP2A and LMP2B were capable of modulating the induction of IFN-stimulated genes in response to
poly(I:C) stimulation. These findings show that LMP2A and LMP2B target multiple effector pathways
involved in innate immune recognition, and that situations may exist during epithelial cell infection where
EBV is required to target one or both of these pathways to achieve stable persistent infection.
EBV Conference 2008 Guangzhou
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