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Journal of Virology, March 2006, p. 2760-2770, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2760-2770.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

ß1 Integrin Mediates Internalization of Mammalian Reovirus

Melissa S. Maginnis,^1,2, J. Craig Forrest,^1,2,, Sarah A. Kopecky-Bromberg,^1,2, S. Kent Dickeson,³ Samuel A. Santoro,³ Mary M. Zutter,³ Glen R. Nemerow,⁴ Jeffrey M. Bergelson,⁵ and Terence S. Dermody^1,2,6*

Departments of Microbiology and Immunology,¹ Pathology,³ Pediatrics,⁶ Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232,² The Scripps Research Institute, La Jolla, California 92037,⁴ Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104⁵

Received 17 October 2005/ Accepted 28 December 2005

Reovirus infection is initiated by interactions between the attachment protein 1 and cell surface carbohydrate and junctional adhesion molecule A (JAM-A). Expression of a JAM-A mutant lacking a cytoplasmic tail in nonpermissive cells conferred full susceptibility to reovirus infection, suggesting that cell surface molecules other than JAM-A mediate viral internalization following attachment. The presence of integrin-binding sequences in reovirus outer capsid protein 2, which serves as the structural base for 1, suggests that integrins mediate reovirus endocytosis. A ß1 integrin-specific antibody, but not antibodies specific for other integrin subunits, inhibited reovirus infection of HeLa cells. Expression of a ß1 integrin cDNA, along with a cDNA encoding JAM-A, in nonpermissive chicken embryo fibroblasts conferred susceptibility to reovirus infection. Infectivity of reovirus was significantly reduced in ß1-deficient mouse embryonic stem cells in comparison to isogenic cells expressing ß1. However, reovirus bound equivalently to cells that differed in levels of ß1 expression, suggesting that ß1 integrins are involved in a postattachment entry step. Concordantly, uptake of reovirus virions into ß1-deficient cells was substantially diminished in comparison to viral uptake into ß1-expressing cells. These data provide evidence that ß1 integrin facilitates reovirus internalization and suggest that viral entry occurs by interactions of reovirus virions with independent attachment and entry receptors on the cell surface.

These authors contributed equally to the manuscript.

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

Present address: Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.

This article has been cited by other articles:

• Maginnis, M. S., Mainou, B. A., Derdowski, A., Johnson, E. M., Zent, R., Dermody, T. S. (2008). NPXY Motifs in the {beta}1 Integrin Cytoplasmic Tail Are Required for Functional Reovirus Entry. J. Virol. 82: 3181-3191 [Abstract] [Full Text]