This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.02574-06v1 81/11/5685    most recent 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 Rojek, J. M. Articles by Kunz, S. Search for Related Content PubMed PubMed Citation Articles by Rojek, J. M. Articles by Kunz, S.

Old World and Clade C New World Arenaviruses Mimic the Molecular Mechanism of Receptor Recognition Used by -Dystroglycan's Host-Derived Ligands

Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037,¹ Howard Hughes Medical Institute, University of Iowa College of Medicine, Department of Molecular Physiology and Biophysics, Department of Neurology, and Department of Internal Medicine, Iowa City, Iowa 52242,² Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333³

Received 21 November 2006/ Accepted 2 March 2007

-Dystroglycan (DG) is an important cellular receptor for extracellular matrix (ECM) proteins and also serves as the receptor for Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) and clade C New World arenaviruses. In the host cell, -DG is subject to a remarkably complex pattern of O glycosylation that is crucial for its interactions with ECM proteins. Two of these unusual sugar modifications, protein O mannosylation and glycan modifications involving the putative glycosyltransferase LARGE, have recently been implicated in arenavirus binding. Considering the complexity of -DG O glycosylation, our present study was aimed at the identification of the specific O-linked glycans on -DG that are recognized by arenaviruses. As previously shown for LCMV, we found that protein O mannosylation of -DG is crucial for the binding of arenaviruses of distinct phylogenetic origins, including LFV, Mobala virus, and clade C New World arenaviruses. In contrast to the highly conserved requirement for O mannosylation, more generic O glycans present on -DG are dispensable for arenavirus binding. Despite the critical role of O-mannosyl glycans for arenavirus binding under normal conditions, the overexpression of LARGE in cells deficient in O mannosylation resulted in highly glycosylated -DG that was functional as a receptor for arenaviruses. Thus, modifications by LARGE but not O-mannosyl glycans themselves are most likely the crucial structures recognized by arenaviruses. Together, the data demonstrate that arenaviruses recognize the same highly conserved O-glycan structures on -DG involved in ECM protein binding, indicating a strikingly similar mechanism of receptor recognition by pathogen- and host-derived ligands.

Published ahead of print on 14 March 2007.

This article has been cited by other articles:

• Rojek, J. M., Sanchez, A. B., Nguyen, N. T., de la Torre, J.-C., Kunz, S. (2008). Different Mechanisms of Cell Entry by Human-Pathogenic Old World and New World Arenaviruses. J. Virol. 82: 7677-7687 [Abstract] [Full Text]  
• Lee, A. M., Rojek, J. M., Spiropoulou, C. F., Gundersen, A. T., Jin, W., Shaginian, A., York, J., Nunberg, J. H., Boger, D. L., Oldstone, M. B. A., Kunz, S. (2008). Unique Small Molecule Entry Inhibitors of Hemorrhagic Fever Arenaviruses. J. Biol. Chem. 283: 18734-18742 [Abstract] [Full Text]  
• Rojek, J. M., Lee, A. M., Nguyen, N., Spiropoulou, C. F., Kunz, S. (2008). Site 1 Protease Is Required for Proteolytic Processing of the Glycoproteins of the South American Hemorrhagic Fever Viruses Junin, Machupo, and Guanarito. J. Virol. 82: 6045-6051 [Abstract] [Full Text]  
• Dylla, D. E., Michele, D. E., Campbell, K. P., McCray, P. B. Jr. (2008). Basolateral Entry and Release of New and Old World Arenaviruses from Human Airway Epithelia. J. Virol. 82: 6034-6038 [Abstract] [Full Text]  
• Rojek, J. M., Perez, M., Kunz, S. (2008). Cellular Entry of Lymphocytic Choriomeningitis Virus. J. Virol. 82: 1505-1517 [Abstract] [Full Text]  
• Rojek, J. M., Campbell, K. P., Oldstone, M. B.A., Kunz, S. (2007). Old World Arenavirus Infection Interferes with the Expression of Functional {alpha}-Dystroglycan in the Host Cell. Mol. Biol. Cell 18: 4493-4507 [Abstract] [Full Text]