Contents - College of Medical and Dental Sciences - University of ...

The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Poster Session Abstract P2
MODULATION OF INTERFERON β GENE EXPRESSION BY KAPOSI’S SARCOMA
ASSOCIATED HERPESVIRUS (KSHV) LATENCY PROTEINS
Nathalie Cloutier and Louis Flamand.
Laboratory of Virology, Rheumatology and Immunology Research Center, CHUQ Research
Center and Faculty of Medicine, Laval University, Quebec, Canada, G1V 4G2.
Abstract
The interferon (IFN) system represents a potent antiviral defense mechanism. KSHV is an
oncogenic virus associated with KS, Primary Effusion Lymphoma and Multicentric
Castleman’s Disease. Latency proteins are important for immune evasion by KSHV from
the host and ensuring viral persistence. Our objective is to determine the impact of v-
FLIP, v-Cyclin and LANA expression on interferon-b synthesis.
Considering that the ifn-b gene is regulated partly through NF-kB, we sought to
determine whether v-FLIP could activate the ifn-b gene. By itself, v-FLIP protein has no
effect on ifn-b gene activation but when combined with IFN-b inducers, a synergistic
activation occurs. This effect is strictly dependent on NF-kB and is mediated through the
positive regulatory domain II of the IFN-b promoter. v-Cyclin has no impact on ifn-b
gene activation. Our preliminary results show that LANA inhibits ifn-b activation.
v-FLIP activates NF-κB and is essential for the survival of infected cells. During the lytic
cycle, dsRNA and dsDNA molecules produced by KSHV replication will activate the
interferon pathway and v-FLIP is likely to potentiate this effect. The synergy between v-
FLIP and the IFN-b inducers will favor IFN-b production by lytically infected cells. On the
other hand, LANA expression dampens this effect by suppressing ifn-b expression.
Studies with infected cells will be important to understand the interplay between latency
proteins and IFN-b production during the replication of KSHV. A balance between
activation and inhibition of the ifn-b gene must occur for infected cells to persist and
avoid elimination by the host immune system defense mechanisms.
Presenting author Email: Nathalie.Cloutier@crchul.ulaval.ca
99