Characterization of the Interaction of Lassa Fever Virus with Its Cellular Receptor α-Dystroglycan

Abstract

The cellular receptor for the Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) has recently been identified as ␣-dystroglycan (␣-DG), a cell surface receptor that provides a molecular link between the extracellular matrix and the actin-based cytoskeleton. In the present study, we show that LFV binds to ␣-DG with high affinity in the low-nanomolar range. Recombinant vesicular stomatitis virus pseudotyped with LFV glycoprotein (GP) adopted the receptor binding characteristics of LFV and depended on ␣-DG for infection of cells. Mapping of the binding site of LFV on ␣-DG revealed that LFV binding required the same domains of ␣-DG that are involved in the binding of LCMV. Further, LFV was found to efficiently compete with laminin ␣1 and ␣2 chains for ␣-DG binding. Together with our previous studies on receptor binding of the prototypic immunosuppressive LCMV isolate LCMV clone 13, these findings indicate a high degree of conservation in the receptor binding characteristics between the highly human-pathogenic LFV and murine-immunosuppressive LCMV isolates.

Unique Small Molecule Entry Inhibitors of Hemorrhagic Fever Arenaviruses

“…After 2 h, the wells were washed and bound virus detected by enzyme-linked immunosorbent assay (24).…”

Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses

“…␣-Dystroglycan is a cellular receptor for New World clade C and Old World arenaviruses (25)(26)(27). Four New World clade B arenaviruses (MACV, JUNV, GTOV, and SABV) use transferrin receptor 1 (TfR1) as a cellular receptor (28).…”

Substitutions in the Glycoprotein (GP) of the Candid#1 Vaccine Strain of Junin Virus Increase Dependence on Human Transferrin Receptor 1 for Entry and Destabilize the Metastable Conformation of GP

“…Two different cellular receptors have been described, ␣-dystroglycan for the Old World and New World clade C viruses (10,30,38) and transferrin receptor type 1 (TfR1) for the New World clade B viruses (35). Binding of GP1 to a receptor results in endocytosis of the viral particle, where exposure to low pH triggers a series of conformational changes in GP2 that lead to fusion (7,11,25).…”