Transferrin receptor is a carrier protein for transferrin. It is needed for the import of iron into the cell and is regulated in response to intracellular iron concentration. Low iron concentrations promote increased levels of transferrin receptor, to increase iron intake into the cell. Thus, transferrin receptor maintains cellular iron homeostasis. Expression of human TFR1, but not human TFR2, in hamster cell lines markedly enhanced the infection of viruses pseudotyped with the glycoprotein of Machupo, Guanarito, and Junin viruses, but not with those of Lassa or lymphocytic choriomeningitis viruses. An anti-TFR1 antibody efficiently inhibited the replication of Machupo, Guanarito, Junin, and Sabia viruses, but not that of Lassa virus.TFR1 is a cellular receptor for New World hemorrhagic fever arenaviruses.