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Journal of Virology, February 2002, p. 1632-1641, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1632-1641.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Virion Disassembly Is Required for Apoptosis Induced by Reovirus

Jodi L. Connolly,{dagger} and Terence S. Dermody*

Departments of Pediatrics and Microbiology and Immunology and Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Received 19 June 2001/ Accepted 19 November 2001

Reovirus infection leads to apoptosis in cultured cells and in vivo. Binding of viral attachment protein {varsigma}1 to both sialic acid and junction adhesion molecule is required for induction of apoptosis. However, it is not known whether viral engagement of receptors is sufficient to elicit this cellular response. To determine whether steps in reovirus replication subsequent to viral attachment are required for reovirus-induced apoptosis, we used inhibitors of viral disassembly and RNA synthesis, viral disassembly intermediates, temperature-sensitive (ts) reovirus mutants, and reovirus particles deficient in genomic double-stranded RNA (dsRNA). We found that reovirus-induced apoptosis is abolished in the presence of the viral disassembly inhibitors ammonium chloride and E64. Infectious subvirion particles (ISVPs), which are intermediates in reovirus disassembly that can be generated in vitro by protease treatment, are capable of inducing apoptosis in the presence or absence of these inhibitors. Treatment of cells with the viral RNA synthesis inhibitor ribavirin does not diminish the capacity of reovirus to induce apoptosis, and reovirus ts mutants arrested at defined steps in viral replication produce apoptosis with efficiency similar to that of wild-type virus. Furthermore, reovirus particles lacking dsRNA are capable of inducing apoptosis. Finally, we found that viral attachment and disassembly must occur within the same cellular compartment for reovirus to elicit an apoptotic response. These results demonstrate that disassembly of reovirus virions to form ISVPs, but not viral transcription or subsequent steps in viral replication, is required for reovirus to induce apoptosis.

* Corresponding author. Mailing address: Lamb Center for Pediatric Research, D7235 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232. Phone: (615) 343-9943. Fax: (615) 343-9723. E-mail: terry.dermody{at}mcmail.vanderbilt.edu.

{dagger} Present address: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037.

Journal of Virology, February 2002, p. 1632-1641, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1632-1641.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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