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Journal of Virology, June 2004, p. 5996-6004, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5996-6004.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cell-Cell Fusion Induced by the Avian Reovirus Membrane Fusion Protein Is Regulated by Protein Degradation

Maya Shmulevitz, Jennifer Corcoran, Jayme Salsman, and Roy Duncan*

Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7

Received 14 September 2003/ Accepted 28 January 2004

The p10 fusion-associated small transmembrane protein of avian reovirus induces extensive syncytium formation in transfected cells. Here we show that p10-induced cell-cell fusion is restricted by rapid degradation of the majority of newly synthesized p10. The small ectodomain of p10 targets the protein for degradation following p10 insertion into an early membrane compartment. Paradoxically, conservative amino acid substitutions in the p10 ectodomain hydrophobic patch that eliminate fusion activity also increase p10 stability. The small amount of p10 that escapes intracellular degradation accumulates at the cell surface in a relatively stable form, where it mediates cell-cell fusion as a late-stage event in the virus replication cycle. The unusual relationship between a nonstructural viral membrane fusion protein and the replication cycle of a nonenveloped virus has apparently contributed to the evolution of a novel mechanism for restricting the extent of virus-induced cell-cell fusion.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7. Phone: (902) 494-6770. Fax: (902) 494-5125. E-mail: roy.duncan{at}dal.ca.


Journal of Virology, June 2004, p. 5996-6004, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5996-6004.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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