Letter

Nature 446, 92-96 (1 March 2007) | doi:10.1038/nature05539; Received 4 November 2006; Accepted 18 December 2006; Published online 7 February 2007

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

Sheli R. Radoshitzky1,7, Jonathan Abraham2,7, Christina F. Spiropoulou3, Jens H. Kuhn1,4, Dan Nguyen2, Wenhui Li1, Jane Nagel1, Paul J. Schmidt5, Jack H. Nunberg6, Nancy C. Andrews5, Michael Farzan1 & Hyeryun Choe2

  1. Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772, USA
  2. Pulmonary Division, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
  3. Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
  4. Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, 14195 Berlin, Germany
  5. Division of Hematology/Oncology, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
  6. Montana Biotechnology Center, The University of Montana, Missoula, Montana 59812, USA
  7. These authors contributed equally to this work.

Correspondence to: Hyeryun Choe2 Correspondence and requests for materials should be addressed to H.C. (Email: hyeryun.choe@childrens.harvard.edu).

At least five arenaviruses cause viral haemorrhagic fevers in humans. Lassa virus, an Old World arenavirus, uses the cellular receptor alpha-dystroglycan to infect cells1. Machupo, Guanarito, Junin and Sabia viruses are New World haemorrhagic fever viruses that do not use alpha-dystroglycan2. 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.

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