Characterization of the cellular receptors for the South American hemorrhagic fever viruses Junin, Guanarito, and Machupo

The New World arenaviruses Junin, Machupo, and Guanarito are the causative agents of hemorrhagic fevers (HF) with high mortality in humans. The cellular receptor for Old World arenaviruses and one subgroup of the New World arenaviruses (Clade C) have been identified as α-dystroglycan (α-DG). In contrast, the receptor(s) of the South American HF viruses, which belong to the Clade B New World arenaviruses, are currently unknown. To begin to characterize the cellular receptors used by these pathogens, we generated recombinant retroviral pseudotypes with the glycoproteins of Guanarito, Junin, and Machupo. Infection with the South American HF viruses is independent of α-DG and functional receptors for Guanarito, Junin, and Machupo were found on most human cell types and cells derived from non-human primate and rodents. Guanarito, Junin, and Machupo share a common receptor, which is distinct from the receptor(s) used by the closely related non-pathogenic Clade B virus Amapari, and the genetically more distant Clade A and C New World arenaviruses. We show that the cellular receptor(s) for the South American HF viruses are proteins or protein-linked entities and that infection is not dependent on protein-linked N-glycans, O-glycans, or glycosaminoglycans.