vFLIP from KSHV inhibits anoikis of primary endothelial cells.
Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) infection of endothelial cells is an early event in the aetiology of the endothelial cell tumour Kaposi's sarcoma (KS). We have examined the effect of the KSHV latent protein viral FLICE-like inhibitory protein (vFLIP) on dermal microvascular endothelial cell (MVEC) survival as vFLIP is expressed in the KSHV-infected cells within KS lesions. To do this, we have used a lentiviral vector to express vFLIP in MVECs in the absence of other KSHV proteins. vFLIP activates the classical NF-kappaB pathway in MVECs and causes nuclear translocation of RelA/p65. This NF-kappaB activation prevents detachment-induced apoptosis (anoikis) of MVECs but does not inhibit apoptosis induced by removal of essential survival factors, including vascular endothelial growth factor (VEGF). vFLIP expression inhibits anoikis in part by inducing the secretion of an additional paracrine survival factor(s). The implications of these results for KS development are discussed.
Efklidou
Sofia
S
Infection and Immunity, University College London, Windeyer Building, London, UK.
Bailey
Ranbir
R
Field
Nigel
N
Noursadeghi
Mahdad
M
Collins
Mary K
MK
D023102:Anoikis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D016328:NF-kappa B; D014764:Viral Proteins; C481275:viral FLIP protein, Human herpesvirus 8