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Journal of Virology, August 2002, p. 7932-7941, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.7932-7941.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Avian Reoviruses Cause Apoptosis in Cultured Cells: Viral Uncoating, but Not Viral Gene Expression, Is Required for Apoptosis Induction

Lucía Labrada,1,{dagger} Gustavo Bodelón,1 Juan Viñuela,2 and Javier Benavente1*

Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela,1 Laboratorio de Immunología, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain2

Received 4 February 2002/ Accepted 10 May 2002

The cytopathic effect evidenced by cells infected with avian reovirus S1133 suggests that this virus may induce apoptosis in primary cultures of chicken embryo fibroblasts. In this report we present evidence that avian reovirus infection of cultured cells causes activation of the intracellular apoptotic program and that this activation takes place during an early stage of the viral life cycle. The ability of avian reoviruses to induce apoptosis is not restricted to a particular virus strain or to a specific cell type, since different avian reovirus isolates were able to induce apoptosis in several avian and mammalian cell lines. Apoptosis was also provoked in ribavirin-treated avian reovirus-infected cells and in cells infected with UV-irradiated reovirions, indicating that viral mRNA synthesis and subsequent steps in viral replication are not needed for apoptosis induction in avian reovirus-infected cells and that the number of inoculated virus particles, not their infectivity, is the critical factor for apoptosis induction by avian reovirus. Our finding that apoptosis is no longer induced when intracellular viral uncoating is blocked indicates that intraendosomal virion disassembly is required for apoptosis induction and that attachment and uptake of parental reovirions are not sufficient to cause apoptosis. Taken together, our results suggest that apoptosis is triggered from within the infected cell by viral products generated after intraendosomal uncoating of parental reovirions.

* Corresponding author. Mailing address: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Phone and fax: 34-981-599157. E-mail: bnjbena{at}usc.es.

{dagger} Present address: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032.

Journal of Virology, August 2002, p. 7932-7941, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.7932-7941.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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