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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
-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
-Dystroglycan (
-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
-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
-DG would be involved in viral receptor function. Here, we demonstrate that glycosylation of
-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.
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