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Journal of Virology, November 2005, p. 14282-14296, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14282-14296.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Posttranslational Modification of {alpha}-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding

Stefan Kunz,1* Jillian M. Rojek,1 Motoi Kanagawa,2 Christina F. Spiropoulou,3 Rita Barresi,2 Kevin P. Campbell,2 and Michael B. A. Oldstone1,4

Departments of Neuropharmacology,1 Infectiology, The Scripps Research Institute, La Jolla, California 92037,4 Howard Hughes Medical Institute, University of Iowa College of Medicine, Department of Physiology and Biophysics, Neurology, Iowa City, Iowa 52242,2 Special Pathogens Branco, Centers for Disease Control and Prevention, Atlanta, Georgia 303333

Received 28 April 2005/ Accepted 17 August 2005

The receptor for lymphocytic choriomeningitis virus (LCMV), the human pathogenic Lassa fever virus (LFV), and clade C New World arenaviruses is {alpha}-dystroglycan ({alpha}-DG), a cell surface receptor for proteins of the extracellular matrix (ECM). Specific posttranslational modification of {alpha}-DG by the glycosyltransferase LARGE is critical for its function as an ECM receptor. In the present study, we show that LARGE-dependent modification is also crucial for {alpha}-DG's function as a cellular receptor for arenaviruses. Virus binding involves the mucin-type domain of {alpha}-DG and depends on modification by LARGE. A crucial role of the LARGE-dependent glycosylation of {alpha}-DG for virus binding is found for several isolates of LCMV, LFV, and the arenaviruses Mobala and Oliveros. Since the posttranslational modification by LARGE is crucial for {alpha}-DG recognition by both arenaviruses and the host-derived ligand laminin, it also influences competition between virus and laminin for {alpha}-DG. Hence, LARGE-dependent glycosylation of {alpha}-DG has important implications for the virus-host cell interaction and the pathogenesis of LFV in humans.

* 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, November 2005, p. 14282-14296, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14282-14296.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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