Cell entry of Lassa virus induces tyrosine phosphorylation of dystroglycan

Summary The extracellular matrix (ECM) receptor dystrogly- can (DG) serves as a cellular receptor for the highly pathogenic arenavirus Lassa virus (LASV) that causes a haemorrhagic fever with high mortality in human. In the host cell, DG provides a molecular linkbetweentheECMandtheactincytoskeletonvia the adapter proteins utrophin or dystrophin. Here we investigated post-translational modifications of DG in the context of LASV cell entry. Using the tyrosine kinase inhibitor genistein, we found that tyrosine kinases are required for efficient internali- zation of virus particles, but not virus-receptor binding. Engagement of cellular DG by LASV enve- lope glycoprotein (LASV GP) in human epithelial cells induced tyrosine phosphorylation of the cyto- plasmic domain of DG. LASV GP binding to DG further resulted in dissociation of the adapter protein utrophin from virus-bound DG. This virus- induced dissociation of utrophin was affected by genistein treatment, suggesting a role of receptor tyrosine phosphorylation in the process.