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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Pathogenesis Abstract 20
ROLE OF K15 IN KAPOSI’S SARCOMA HERPESVIRUS INDUCED ENDOTHELIAL
CELL MIGRATION
Bernd Hillenbrand, Antje Bürger, Irina Fischer, Khaled Alkharsah and Thomas F. Schulz
Institute of Virology, Hanover Medical School, Hanover, 30625, Germany
Abstract
Kaposi’s sarcoma herpesvirus (KSHV) is the cause of Kaposi’s sarcoma, a highly
vascularized tumour. Others have previously proposed a role for IL-8 in endothelial cell
migration induced by KSHV-infected cells (Lane et al., J.Virol. 2002; 76:11570-11583).
We previously showed that the K15 protein of KSHV induces increased IL-8 secretion in
epithelial cells. In this study we addressed the role of K15 for virus induced endothelial
cell migration in the context of the whole viral genome. We constructed a K15 deficient
recombinant virus genome (KSHVΔK15) by using a bacterial artificial chromosome (BAC)
system. We generated stable HEK293 cells carrying the BAC36 (wt) or BAC ΔK15.
Following the induction of the lytic replication cycle reduced IL-8 mRNA levels were found
by gene expression microarray in BAC ΔK15 cells in comparison to BAC36 cells. This
reduction was confirmed by IL-8 specific ELISA of BAC36 and BAC ΔK15 conditioned
media. In endothelial cell migration assays the migration of primary human vascular
endothelial cells (HUVEC) in response to conditioned culture supernatants from KSHV
ΔK15-infected cells was significantly reduced in comparison to supernatants from
KSHVwt-infected cells. In contrast, supernatants from cells infected with a recombinant
KSHV lacking the viral FLIP (BAC ΔFLIP), like K15 an inducer of NFκB, induced the same
degree of endothelial cell migration as KSHVwt–infected cells. These results suggest an
involvement of K15 in KSHV induced endothelial cell migration and possibly angiogenesis.
Presenting author Email: hillenbrand.bernd@mh-hannover.de
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