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Journal of Virology, May 2005, p. 5979-5987, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.5979-5987.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Characterization of the Interaction of Lassa Fever Virus with Its Cellular Receptor {alpha}-Dystroglycan

Stefan Kunz,1* Jillian M. Rojek,1 Mar Perez,1 Christina F. Spiropoulou,2 and Michael B. A. Oldstone1

Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037,1 Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 303332

Received 30 September 2004/ Accepted 23 December 2004

The cellular receptor for the Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) has recently been identified as {alpha}-dystroglycan ({alpha}-DG), a cell surface receptor that provides a molecular link between the extracellular matrix and the actin-based cytoskeleton. In the present study, we show that LFV binds to {alpha}-DG with high affinity in the low-nanomolar range. Recombinant vesicular stomatitis virus pseudotyped with LFV glycoprotein (GP) adopted the receptor binding characteristics of LFV and depended on {alpha}-DG for infection of cells. Mapping of the binding site of LFV on {alpha}-DG revealed that LFV binding required the same domains of {alpha}-DG that are involved in the binding of LCMV. Further, LFV was found to efficiently compete with laminin {alpha}1 and {alpha}2 chains for {alpha}-DG binding. Together with our previous studies on receptor binding of the prototypic immunosuppressive LCMV isolate LCMV clone 13, these findings indicate a high degree of conservation in the receptor binding characteristics between the highly human-pathogenic LFV and murine-immunosuppressive LCMV isolates.

* Corresponding author. Mailing address: Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-9447. Fax: (858) 784-9981. E-mail: stefanku{at}scripps.edu.

Journal of Virology, May 2005, p. 5979-5987, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.5979-5987.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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