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Journal of Virology, September 2000, p. 8135-8139, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Reovirus-Induced Apoptosis Is Mediated by TRAIL

Penny Clarke,1 Suzanne M. Meintzer,1 Spencer Gibson,2,3 Christian Widmann,2,3 Timothy P. Garrington,2,3 Gary L. Johnson,2,3,4 and Kenneth L. Tyler1,5,6,*

Departments of Neurology,1 Pharmacology,4 and Medicine, Microbiology and Immunology,5 University of Colorado Health Sciences Center, and Denver Veteran's Affairs Medical Center,6 Denver, Colorado 80262, and Program in Molecular Signal Transduction2 and Division of Basic Sciences,3 National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206

Received 13 April 2000/Accepted 9 June 2000

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.

* Corresponding author. Mailing address: Department of Neurology (127), Denver VA Medical Center, 1066 Clermont St., Denver, CO 80220. Phone: (303) 393-2874. Fax: (303) 393-4686. E-mail: Ken.Tyler{at}uchsc.edu.

Journal of Virology, September 2000, p. 8135-8139, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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