Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses.
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.
Radoshitzky
Sheli R
SR
Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772, USA.
Abraham
Jonathan
J
Spiropoulou
Christina F
CF
Kuhn
Jens H
JH
Nguyen
Dan
D
Li
Wenhui
W
Nagel
Jane
J
Schmidt
Paul J
PJ
Nunberg
Jack H
JH
Andrews
Nancy C
NC
Farzan
Michael
M
Choe
Hyeryun
H
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
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