This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Danthi, P. Articles by Dermody, T. S. Search for Related Content PubMed PubMed Citation Articles by Danthi, P. Articles by Dermody, T. S.

 Previous Article  |  Next Article 

Journal of Virology, February 2006, p. 1261-1270, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1261-1270.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

JAM-A-Independent, Antibody-Mediated Uptake of Reovirus into Cells Leads to Apoptosis

Pranav Danthi,^1,2 Mark W. Hansberger,^2,3 Jacquelyn A. Campbell,^2,3 J. Craig Forrest,^2,3, and Terence S. Dermody^1,2,3*

Departments of Pediatrics,¹ Microbiology and Immunology,³ Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232²

Received 1 September 2005/ Accepted 31 October 2005

Apoptosis plays a major role in the cytopathic effect induced by reovirus following infection of cultured cells and newborn mice. Strain-specific differences in the capacity of reovirus to induce apoptosis segregate with the S1 and M2 gene segments, which encode attachment protein 1 and membrane penetration protein µ1, respectively. Virus strains that bind to both junctional adhesion molecule-A (JAM-A) and sialic acid are the most potent inducers of apoptosis. In addition to receptor binding, events in reovirus replication that occur during or after viral disassembly but prior to initiation of viral RNA synthesis also are required for reovirus-induced apoptosis. To determine whether reovirus infection initiated in the absence of JAM-A and sialic acid results in apoptosis, Chinese hamster ovary (CHO) cells engineered to express Fc receptors were infected with reovirus using antibodies directed against viral outer-capsid proteins. Fc-mediated infection of CHO cells induced apoptosis in a 1-independent manner. Apoptosis following this uptake mechanism requires acid-dependent proteolytic disassembly, since treatment of cells with the weak base ammonium chloride diminished the apoptotic response. Analysis of T1L x T3D reassortant viruses revealed that the µ1-encoding M2 gene segment is the only viral determinant of the apoptosis-inducing capacity of reovirus when infection is initiated via Fc receptors. Additionally, a temperature-sensitive, membrane penetration-defective M2 mutant, tsA279.64, is an inefficient inducer of apoptosis. These data suggest that signaling pathways activated by binding of 1 to JAM-A and sialic acid are dispensable for reovirus-mediated apoptosis and that the µ1 protein plays an essential role in stimulating proapoptotic signaling.

Present address: Department of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.

This article has been cited by other articles:

• Danthi, P., Kobayashi, T., Holm, G. H., Hansberger, M. W., Abel, T. W., Dermody, T. S. (2008). Reovirus Apoptosis and Virulence Are Regulated by Host Cell Membrane Penetration Efficiency. J. Virol. 82: 161-172 [Abstract] [Full Text]  
• Hansberger, M. W., Campbell, J. A., Danthi, P., Arrate, P., Pennington, K. N., Marcu, K. B., Ballard, D. W., Dermody, T. S. (2007). I{kappa}B Kinase Subunits {alpha} and {gamma} Are Required for Activation of NF-{kappa}B and Induction of Apoptosis by Mammalian Reovirus. J. Virol. 81: 1360-1371 [Abstract] [Full Text]  
• Coffey, C. M., Sheh, A., Kim, I. S., Chandran, K., Nibert, M. L., Parker, J. S. L. (2006). Reovirus Outer Capsid Protein {micro}1 Induces Apoptosis and Associates with Lipid Droplets, Endoplasmic Reticulum, and Mitochondria.. J. Virol. 80: 8422-8438 [Abstract] [Full Text]