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Journal of Virology, September 2006, p. 8422-8438, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.02601-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Reovirus Outer Capsid Protein µ1 Induces Apoptosis and Associates with Lipid Droplets, Endoplasmic Reticulum, and Mitochondria

Caroline M. Coffey,1 Alexander Sheh,1,{dagger} Irene S. Kim,2,{ddagger} Kartik Chandran,2,§ Max L. Nibert,2* and John S. L. Parker1*

Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853,1 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 021152

Received 14 December 2005/ Accepted 7 June 2006

The mechanisms by which reoviruses induce apoptosis have not been fully elucidated. Earlier studies identified the mammalian reovirus S1 and M2 genes as determinants of apoptosis induction. However, no published results have demonstrated the capacities of the proteins encoded by these genes to induce apoptosis, either independently or in combination, in the absence of reovirus infection. Here we report that the mammalian reovirus µ1 protein, encoded by the M2 gene, was sufficient to induce apoptosis in transfected cells. We also found that µ1 localized to lipid droplets, endoplasmic reticulum, and mitochondria in both transfected cells and infected cells. Two small regions encompassing amphipathic {alpha}-helices within a carboxyl-terminal portion of µ1 were necessary for efficient induction of apoptosis and association with lipid droplets, endoplasmic reticulum, and mitochondria in transfected cells. Induction of apoptosis by µ1 and its association with lipid droplets and intracellular membranes in transfected cells were abrogated when µ1 was coexpressed with {sigma}3, with which it is known to coassemble. We propose that µ1 plays a direct role in the induction of apoptosis in infected cells and that this property may relate to the capacity of µ1 to associate with intracellular membranes. Moreover, during reovirus infection, association with {sigma}3 may regulate apoptosis induction by µ1.

* Corresponding author. Mailing address for John S. L. Parker: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Hungerford Hill Road, Ithaca, NY 14853. Phone: (607) 256-5626. Fax: (607) 256-5608. E-mail: jsp7{at}cornell.edu. Mailing address for Max L. Nibert: Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 645-3680. Fax: (617) 738-7664. E-mail: mnibert{at}hms.harvard.edu.

{dagger} Present address: Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139.

{ddagger} Present address: Training Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA 02115.

§ Present address: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.

Journal of Virology, September 2006, p. 8422-8438, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.02601-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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