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

 Previous Article  |  Next Article 

Journal of Virology, November 2005, p. 14297-14308, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14297-14308.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

O Mannosylation of {alpha}-Dystroglycan Is Essential for Lymphocytic Choriomeningitis Virus Receptor Function

Mauro Imperiali,1 Claudio Thoma,1 Ernesto Pavoni,2 Andrea Brancaccio,2 Nico Callewaert,1 and Annette Oxenius1*

Institute for Microbiology, ETH Zurich, 8093 Zürich, Switzerland,1 CNR, Istituto di Chimica del Riconoscimento Molecolare c/o Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy2

Received 25 April 2005/ Accepted 23 August 2005

{alpha}-Dystroglycan ({alpha}-DG) was identified as a common receptor for lymphocytic choriomeningitis virus (LCMV) and several other arenaviruses including the human pathogenic Lassa fever virus. Initial work postulated that interactions between arenavirus glycoproteins and {alpha}-DG are based on protein-protein interactions. We found, however, that susceptibility toward LCMV infection differed in various cell lines despite them expressing comparable levels of DG, suggesting that posttranslational modifications of {alpha}-DG would be involved in viral receptor function. Here, we demonstrate that glycosylation of {alpha}-DG, and in particular, O mannosylation, which is a rare type of O-linked glycosylation in mammals, is essential for LCMV receptor function. Cells that are defective in components of the O-mannosylation pathway showed strikingly reduced LCMV infectibility. As defective O mannosylation is associated with severe clinical symptoms in mammals such as congenital muscular dystrophies, it is likely that LCMV and potentially other arenaviruses may have selected this conserved and crucial posttranslational modification as the primary target structure for cell entry and infection.


* Corresponding author. Mailing address: ETH-Hönggerberg HCI 4 G401, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland. Phone: 41 1 632 3317. Fax: 41 1 632 10 98. E-mail: oxenius{at}micro.biol.ethz.ch.


Journal of Virology, November 2005, p. 14297-14308, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14297-14308.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Aguilan, J. T, Sundaram, S., Nieves, E., Stanley, P. (2009). Mutational and functional analysis of Large in a novel CHO glycosylation mutant. Glycobiology 19: 971-986 [Abstract] [Full Text]  
  • Cosset, F.-L., Marianneau, P., Verney, G., Gallais, F., Tordo, N., Pecheur, E.-I., ter Meulen, J., Deubel, V., Bartosch, B. (2009). Characterization of Lassa Virus Cell Entry and Neutralization with Lassa Virus Pseudoparticles. J. Virol. 83: 3228-3237 [Abstract] [Full Text]  
  • Imperiali, M., Sporri, R., Hewitt, J., Oxenius, A. (2008). Post-translational modification of {alpha}-dystroglycan is not critical for lymphocytic choriomeningitis virus receptor function in vivo. J. Gen. Virol. 89: 2713-2722 [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]  
  • Rojek, J. M., Spiropoulou, C. F., Campbell, K. P., Kunz, S. (2007). Old World and Clade C New World Arenaviruses Mimic the Molecular Mechanism of Receptor Recognition Used by {alpha}-Dystroglycan's Host-Derived Ligands. J. Virol. 81: 5685-5695 [Abstract] [Full Text]  
  • Eschli, B., Quirin, K., Wepf, A., Weber, J., Zinkernagel, R., Hengartner, H. (2006). Identification of an N-Terminal Trimeric Coiled-Coil Core within Arenavirus Glycoprotein 2 Permits Assignment to Class I Viral Fusion Proteins.. J. Virol. 80: 5897-5907 [Abstract] [Full Text]  
  • Barresi, R., Campbell, K. P. (2006). Dystroglycan: from biosynthesis to pathogenesis of human disease. J. Cell Sci. 119: 199-207 [Abstract] [Full Text]  
  • Kunz, S., Rojek, J. M., Kanagawa, M., Spiropoulou, C. F., Barresi, R., Campbell, K. P., Oldstone, M. B. A. (2005). Posttranslational Modification of {alpha}-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding. J. Virol. 79: 14282-14296 [Abstract] [Full Text]