Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses

Sheli R. Radoshitzky, Jonathan Abraham, Christina F. Spiropoulou, Jens H. Kuhn, Dan Nguyen, Wenhui Li, Jane Nagel, Paul J. Schmidt, Jack H. Nunberg, Nancy C. Andrews, Michael Farzan, Hyeryun Choe

Research output: Contribution to journalArticlepeer-review

346 Scopus citations

Abstract

At least five arenaviruses cause viral haemorrhagic fevers in humans. Lassa virus, an Old World arenavirus, uses the cellular receptor α-dystroglycan to infect cells. Machupo, Guanarito, Junin and Sabia viruses are New World haemorrhagic fever viruses that do not use α-dystroglycan. Here we show a specific, high-affinity association between transferrin receptor 1 (TfR1) and the entry glycoprotein (GP) of Machupo virus. Expression of human TfR1, but not human transferrin receptor 2, in hamster cell lines markedly enhanced the infection of viruses pseudotyped with the GP 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. Iron depletion of culture medium enhanced, and iron supplementation decreased, the efficiency of infection by Junin and Machupo but not Lassa pseudoviruses. These data indicate that TfR1 is a cellular receptor for New World haemorrhagic fever arenaviruses.

Original languageEnglish
Pages (from-to)92-96
Number of pages5
JournalNature
Volume446
Issue number7131
DOIs
StatePublished - Mar 1 2007

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