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PMID: 15067035 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retracted Publication

KSHV vFLIP is essential for the survival of infected lymphoma cells.

The Journal of experimental medicine ·Vol. 199 ·No. 7 ·2004-04-05 ·Pages 993-1003

Guasparri I, Keller SA, Cesarman E

Abstract

Primary effusion lymphomas (PELs) associated with infection by the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) have constitutive nuclear factor (NF)-kappaB activity that is essential for their survival, but the source of this activity is unknown. We report that viral FADD-like interleukin-1-beta-converting enzyme [FLICE/caspase 8]-inhibitory protein (FLIP) activates NF-kappaB more potently than cellular FLIP in B cells and that it is largely responsible for NF-kappaB activation in latently infected PEL cells. Elimination of vFLIP production in PEL cells by RNA interference results in significantly decreased NF-kappaB activity, down-regulation of essential NF-kappaB-regulated cellular prosurvival factors, induction of apoptosis, and enhanced sensitivity to external apoptotic stimuli. vFLIP is the first virally encoded gene shown to be essential for the survival of naturally infected tumor cells.

MeSH Terms
Apoptosis/genetics Base Sequence Cell Line, Tumor Cell Survival Genes, Viral Herpesviridae Infections/pathology,virology Herpesvirus 8, Human/genetics,pathogenicity,physiology Humans Lymphoma/pathology,virology Models, Biological NF-kappa B/metabolism RNA Interference RNA, Small Interfering/genetics Viral Proteins/genetics,physiology
Chemicals
NF-kappa B RNA, Small Interfering Viral Proteins viral FLIP protein, Human herpesvirus 8
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Guasparri Ilaria
Weill Medical College of Cornell University, New York, NY 10021, USA.
Keller Shannon A
Cesarman Ethel
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20031467
Published
2004-04-05
Pages
993-1003
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2211879
Subset
IM
Grants
NCI NIH HHS · R01 CA068939 · United States
NCI NIH HHS · R29 CA068939 · United States
NCI NIH HHS · CA68939 · United States
Corrections
ErratumIn
-
RetractionIn
PMID: 33599700
External Links
PubMed source DOI: 10.1084/jem.20031467 PMC Full Text View journal details
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