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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Virus-Cell Interactions II Abstract 58
CHARACTERISATION OF ENDOPLASMIC RETICULUM (ER) STRESS INDUCERS
THAT LEAD TO KSHV REACTIVATION FROM LATENCY; IDENTIFYING
PHYSIOLOGICAL TRIGGERS?
Lucy Dalton-Griffin, Ed Tsao and Paul Kellam
MRC centre for Medical Molecular virology, Department of Infection,
University College London, 46 Cleveland Street, London, W1T 4JF, UK
Abstract
Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) like other herpesviruses has two stages
to its life cycle; latency and lytic replication. KSHV is known to be required for
development of Kaposi’s Sarcoma, a tumour of endothelial origin and is associated with
the B-cell tumours, Primary Effusion Lymphomas (PELs) and the B-cell polyclonal
expansion Multicentric Castleman’s Disease (MCD). Recently we and others have shown
that the transcription factor X-box binding protein-1 (XBP-1) is a physiological trigger of
KSHV lytic reactivation in PEL. XBP-1 is responsible for the terminal differentiation of Bcells
into plasma cells (PCs) as it is a major regulator of the unfolded protein response
(UPR) and therefore allows production of large quantities of immunoglobulin in these
cells. We have previously shown that PEL are blocked in differentiation by the absence of
active XBP-1; when provided the PEL cells differentiate towards a PC and induce KSHV
lytic replication. Using an RFP lytic reactivation reporter assay we show that the ER stress
inducer DTT activates the KSHV lytic cycle in an XBP-1 dependent manner. Recent
studies have also indicated a role for hypoxia in reactivation via the hypoxia inducible
factors (HIFs). Hypoxia can also result in XBP-1 activation as it is an ER stress inducer.
Here we have investigated the roles of HIF-1α, HIF-2α and XBP-1 in activating the KSHV
lytic cycle.
Presenting author Email: ucbclda@ucl.ac.uk
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