The human herpes virus 8–encoded viral FLICE inhibitory protein protects against growth factor withdrawal–induced apoptosis via NF-κB activation

Publisher Website
Google Scholar
Abstract
The human herpes virus 8 (HHV8)–encoded viral FLICE (Fas-associating protein with death domain–like interleukin-1–converting enzyme) inhibitory protein (vFLIP) is believed to protect cells against death receptor–mediated apoptosis. In the present study we demonstrate that expression of HHV8 vFLIP in a growth factor–dependent TF-1 leukemia cell line protects against growth factor withdrawal–induced apoptosis. Unlike vector-expressing cells, those expressing HHV8 vFLIP maintain their mitochondrial membrane potential upon withdrawal from growth factor and also exhibit a block in the activation of caspases. The protective effect of HHV8 vFLIP is associated with its ability to activate the nuclear factor–κ B (NF-κB) pathway and is missing in the vFLIP encoded by equine herpes virus 2 that lacks this activity. Inhibition of the NF-κB pathway by IκB superrepressor, lactacystin, MG132, arsenic trioxide, and phenylarsine oxide reverse the protection against growth factor withdrawal–induced apoptosis conferred by HHV8 vFLIP. HHV8 vFLIP up-regulates the expression of Bcl-xL, an antiapoptotic member of the Bcl2 family, which is a known target of the NF-κB pathway. Collectively, the above results suggest that HHV8 vFLIP–induced NF-κB activation may contribute to cellular transformation seen in association with HHV8 infection by preventing the apoptosis of cells destined to die because of growth factor deprivation.