Reovirus-Induced Apoptosis Is Mediated by TRAIL

Abstract

Members of the tumor necrosis factor (TNF) receptor superfamily and their activating ligands transmit apoptotic signals in a variety of systems. We now show that the binding of TNF-related, apoptosis-inducing ligand (TRAIL) to its cellular receptors DR5 (TRAILR2) and DR4 (TRAILR1) mediates reovirus-induced apoptosis. Anti-TRAIL antibody and soluble TRAIL receptors block reovirus-induced apoptosis by preventing TRAIL-receptor binding. In addition, reovirus induces both TRAIL release and an increase in the expression of DR5 and DR4 in infected cells. Reovirus-induced apoptosis is also blocked following inhibition of the death receptor-associated, apoptosis-inducing molecules FADD (for FAS-associated death domain) and caspase 8. We propose that reovirus infection promotes apoptosis via the expression of DR5 and the release of TRAIL from infected cells. Virus-induced regulation of the TRAIL apoptotic pathway defines a novel mechanism for virus-induced apoptosis.

Cytotoxic Activity of Human Dendritic Cells Is Differentially Regulated by Double-Stranded RNA and CD40 Ligand

“…Among the molecule known to induce apoptotic cell death, TRAIL has received great attention because of its potential therapeutic applications. Indeed, it was reported that TRAIL specifically induces apoptosis in virus-infected cells (23,24) and tumoral cells (13,14,(25)(26)(27) with minimal cytotoxicity toward normal tissues in vivo (28). These results suggest that TRAIL-expressing DCs may operate in vivo like innate effector cells that induce virus-infected and tumoral cell apoptosis.…”

Expression pattern and transcriptional regulatory mechanism of noxa gene in grass carp (Ctenopharyngodon idella)

“…Thus, as a pro-apoptotic protein, mRNA expression level of noxa was down-regulated. However, the host could response to virus infection and cell apoptosis occurred at the late stage as a self-protection mechanism to limit the spread of progeny virus [24]. Therefore, it is not surprise that the mRNA expression level of noxa was up-regulated at the late stage of infection.…”

Differential Effects of Interleukin-7 and Interleukin-15 on NK Cell Anti-Human Immunodeficiency Virus Activity

“…The findings that (i) NK cells can mediate cytotoxicity by TRAIL (7,32,35,54,63,65,77), (ii) that IL-15 potentiates NK cell cytolytic activity, and (iii) that TRAIL has intrinsic activity against a variety of virally infected targets (5,11,14,17,21,34,41,45,46,73,76) suggest a role for IL-15 to potentiate TRAIL-mediated NK cell viricidal activity. We demonstrate that PBL and resting memory cells from infected individuals express high levels of the TRAIL death receptors and undergo cell death following TRAIL treatments (29,33,45), suggesting that these cells are potential targets for TRAIL killing.…”