title: Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses.
abstract: At least five arenaviruses cause viral haemorrhagic fevers in humans. Lassa virus, an Old World arenavirus, uses the cellular receptor alpha-dystroglycan to infect cells. Machupo, Guanarito, Junin and Sabia viruses are New World haemorrhagic fever viruses that do not use alpha-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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772, USA.
authors.forename: Sheli R
authors.initials: SR
authors.lastname: Radoshitzky
authors.forename: Jonathan
authors.initials: J
authors.lastname: Abraham
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
authors.forename: Dan
authors.initials: D
authors.lastname: Nguyen
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.forename: Jane
authors.initials: J
authors.lastname: Nagel
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Schmidt
authors.forename: Jack H
authors.initials: JH
authors.lastname: Nunberg
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Andrews
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
authors.forename: Hyeryun
authors.initials: H
authors.lastname: Choe
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006477:Arenaviruses, New World / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D003470:Culture Media / Q000737:chemistry; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000032:analysis / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000906:Antibodies; D015703:Antigens, CD; C068126:CD71 antigen; D003470:Culture Media; D006023:Glycoproteins; D011990:Receptors, Transferrin; D011991:Receptors, Virus; C503640:TFR2 protein, human; D014759:Viral Envelope Proteins; D007501:Iron