NDLI: Deletion of Kaposi's Sarcoma-Associated Herpesvirus FLICE Inhibitory Protein, vFLIP, from the Viral Genome Compromises the Activation of STAT1-Responsive Cellular Genes and Spindle Cell Formation in Endothelial Cells ▿

Content Provider	PubMed Central
Author	Alkharsah, Khaled R. Singh, Vivek Vikram Bosco, Raffaella Susann, Santag Adam, Grundhoff Konrad, Andreas Michael, Stürzl Wirth, Dagmar Oliver, Dittrich-breiholz Kracht, Michael Schulz, Thomas F.
Copyright Year	2011
Abstract	Kaposi's sarcoma herpesvirus (KSHV) Fas-associated death domain (FADD)-like interleukin-1 beta-converting enzyme (FLICE)-inhibitory protein, vFLIP, has antiapoptotic properties, is a potent activator of the NF-κB pathway, and induces the formation of endothelial spindle cells, the hallmark of Kaposi's sarcoma, when overexpressed in primary endothelial cells. We used a reverse genetics approach to study several functions of KSHV vFLIP in the context of the whole viral genome. Deletion of the gene encoding vFLIP from a KSHV genome cloned in a bacterial artificial chromosome (BAC) reduced the ability of the virus to persist and induce spindle cell formation in primary human umbilical vein endothelial cells (HUVECs). Only a few, mainly interferon (IFN)-responsive, genes were expressed in wild-type KSHV (KSHV-wt)-infected endothelial cells at levels higher than those in KSHV-ΔFLIP-infected endothelial cells, in contrast to the plethora of cellular genes induced by overexpressed vFLIP. In keeping with this observation, vFLIP induces the phosphorylation of STAT1 and STAT2 in an NF-κB-dependent manner in endothelial cells. vFLIP-dependent phosphorylation of STAT1 and STAT2 could be demonstrated after endothelial cells were infected with KSHV-wt, KSHV-ΔFLIP, and a KSHV-vFLIP revertant virus. These findings document the impact of KSHV vFLIP on the transcriptome of primary endothelial cells during viral persistence and highlight the role of vFLIP in the activation of STAT1/STAT2 and STAT-responsive cellular genes by KSHV.
Related Links	http://dx.doi.org/10.1128/JVI.00226-11
Starting Page	10375
File Format	PDF
ISSN	10985514
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	19
Volume Number	85
Language	English
Publisher	American Society for Microbiology
Publisher Date	2011-10-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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