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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Poster Session Abstract P3
SEVERE CHANGES OF PHENOTYPE AND CYTOKINE EXPRESSION IN KSHV-
INFECTED B-LYMPHOCYTES
Guergana Iotzova 1 , Georg Malterer 1 , Kai Bratke 2 , Werner Luttmann 2 , Antoine Gessain 3 ,
Christine S. Falk 4 , Kevin Robertson 5 , Peter Ghazal 5 and Jürgen Haas 1,5
1 Max-von-Pettenkofer Institute, Ludwig-Maximilians-Universität München; 2 Department
of Pneumology, University Hospital, Rostock; 3 Unit of Epidemiology and Physiopathology
of Oncogenic Viruses, Institut Pasteur, Paris; 4 Institute for Molecular Immunology,
Helmholtz Zentrum München; 5 Division of Pathway Medicine, University of Edinburgh,
Edinburgh
Abstract
KSHV is involved in the pathogenesis of Kaposi´s sarcoma (KS) and B-cell derived
primary effusion lymphomas (PEL). The aim of this study was to systematically
investigate the influence of KSHV infection on the expression of cellular genes in B
lymphocytes. To study these changes, a microarray analysis was performed with
persistently in vitro KSHV-infected B-cells from several donors. A considerable number of
genes (408) were found to be modulated more than 4-fold by KSHV infection: 67.4% of
these genes were downregulated and 32.6% upregulated. Intriguingly, many
downregulated genes encoded for B-cell surface markers and B-cell specific transcription
factors (PAX-5, Oct-2 and Spi-B), which was confirmed on the protein level. The massive
loss of B-cell surface markers or “null” phenotype was similar to PEL tumor cells
suggesting that the loss of B-cell identity is caused by KSHV rather than cellular factors.
KSHV-infected cells could not be lysed by allo-reactive cytotoxic T-cells, indicating that
the null phenotype is associated with immune evasion. The downregulation of the Tolllike
receptors TLR7, TLR9 and TLR10, which was confirmed by real-time PCR, might
contribute to the immune escape of KSHV-infected B-cells. On the other hand, we
detected a marked upregulation of Granzyme A (GzmA) transcripts in KSHV-infected
cells, as well as exceedingly high levels of secreted GzmA in supernatants of KSHVinfected
B-cells and in effusion fluids of PEL patients. shRNA knockdown studies revealed
that GzmA participitates in a parakrine cytokine by inducing cellular IL-10, indicating a
potential role of GzmA in the pathogenesis of KSHV-related PEL.
Presenting author Email: malterer@mvp.uni-muenchen.de
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