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MBC in Press, published online ahead of print August 29, 2007
Mol. Biol. Cell 10.1091/mbc.E07-04-0374

A more recent version of this article appeared on November 1, 2007
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Submitted on April 25, 2007
Revised on August 2, 2007
Accepted on August 22, 2007

Old World Arenavirus Infection Interferes with the Expression of Functional {alpha}-Dystroglycan in the Host Cell

Jillian M. Rojek,* Kevin P. Campbell,{dagger} Michael B.A. Oldstone,* and Stefan Kunz*

*Viral Immunobiology Laboratory, Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037; {dagger}Howard Hughes Medical Institute and Departments of Molecular Physiology and Biophysics, Neurology, and Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242

Monitoring Editor: Jean Schwarzbauer

Alpha-dystroglycan ({alpha}-DG) is an important cellular receptor for extracellular matrix (ECM) proteins as well as the Old World arenaviruses lymphocytic choriomeningitis virus (LCMV) and the human pathogenic Lassa fever virus (LFV). Specific O-glycosylation of {alpha}-DG is critical for its function as receptor for ECM proteins and arenaviruses. Here we investigated the impact of arenavirus infection on {alpha}-DG expression. Infection with an immunosuppressive LCMV isolate caused a marked reduction in expression of functional {alpha}-DG without affecting biosynthesis of DG core protein or global cell surface glycoprotein expression. The effect was caused by the viral glycoprotein (GP) and critically depended on {alpha}-DG binding affinity and GP maturation. An equivalent effect was observed with LFVGP. Viral GP was found to associate with a complex between DG and the glycosyltransferase LARGE in the Golgi. Overexpression of LARGE restored functional {alpha}-DG expression in infected cells. We provide evidence that virus-induced down-modulation of functional {alpha}-DG perturbs DG-mediated assembly of laminin at the cell surface, affecting normal cell-matrix interactions.

Address correspondence to: Stefan Kunz (stefanku{at}scripps.edu)




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J. M. Rojek, A. M. Lee, N. Nguyen, C. F. Spiropoulou, and S. Kunz
Site 1 Protease Is Required for Proteolytic Processing of the Glycoproteins of the South American Hemorrhagic Fever Viruses Junin, Machupo, and Guanarito
J. Virol., June 15, 2008; 82(12): 6045 - 6051.
[Abstract] [Full Text] [PDF]


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