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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Virus-Cell Interactions I Abstract 25
ROLE OF DEFECTIVE OCT-2 AND OCA-B EXPRESSION IN IMMUNOGLOBULIN
PRODUCTION AND KSHV LYTIC REACTIVATION IN PRIMARY EFFUSION
LYMPHOMA
Daniel DiBartolo 1 , Elizabeth Hyjek 1 , Shannon Keller 1 , Ilaria Guasparri 1 , Ren Sun 2 , Amy
Chadburn 1 , Daniel M Knowles 1 , and Ethel Cesarman 1
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New
York, NY, 1 Molecular Biology IDP, University of California at Los Angeles, Los Angeles,
CA 2
Abstract
PEL cells do not express surface or cytoplasmic immunoglobulin (Ig) despite having a
genotype and gene expression signature of highly differentiated B cells. We show the
lack of Oct-2 and OCA-B transcription factors to be responsible, at least in part, for this
defect in Ig production. ORF50/Rta, the major regulator of KSHV lytic reactivation,
contains an octamer motif within its promoter. Thus, we also examined the impact that
the lack of Oct-2 and OCA-B have on lytic reactivation mediated by ORF50. Previous
studies had shown that binding of Oct-1 to the ORF50 promoter significantly enhances
ORF50 transactivation. However, we found that Oct-2, on the other hand, inhibits ORF50
expression and consequently lytic reactivation. Chromatin immunoprecipitation assays
showed that endogenous Oct-1 associates with ORF50 promoter in uninduced cells and
transfection of ORF50 further enhances its binding. Using PEL cells with inducible Oct-2
expression we found that induction of Oct-2 results in Oct-2 association with the ORF50
promoter and decreased Oct-1 binding suggesting that Oct-2 competes with Oct-1 for the
octamer site in the ORF50 promoter, explaining mechanistically the observed inhibitory
effect on lytic reactivation. The consistent absence of Oct-2 in PEL leads us to speculate
that this deficiency is selected for in order to maintain the ability to efficiently transition
from latency to lytic reactivation.
Presenting author Email: ecesarm@med.cornell.edu
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