Transferrin Receptor 1 is a Cellular Receptor for New World Haemorrhagic Fever Arenaviruses

Overview

Journal Nature

Specialty Science

Date 2007 Feb 9

PMID 17287727

Citations 264

Authors

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

Affiliations

Soon will be listed here.

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.

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References

Oldstone M . Arenaviruses. II. The molecular pathogenesis of arenavirus infections. Introduction. Curr Top Microbiol Immunol. 2002; 263:V-XII. View

Reignier T, Oldenburg J, Noble B, Lamb E, Romanowski V, Buchmeier M . Receptor use by pathogenic arenaviruses. Virology. 2006; 353(1):111-20. DOI: 10.1016/j.virol.2006.05.018. View

Oldstone M . Arenaviruses. I. The epidemiology molecular and cell biology of arenaviruses. Introduction. Curr Top Microbiol Immunol. 2002; 262:V-XII. View

Spiropoulou C, Kunz S, Rollin P, Campbell K, Oldstone M . New World arenavirus clade C, but not clade A and B viruses, utilizes alpha-dystroglycan as its major receptor. J Virol. 2002; 76(10):5140-6. PMC: 136162. DOI: 10.1128/jvi.76.10.5140-5146.2002. View

Raya G, Henny J, Steinmetz J, Herbeth B, Siest G . Soluble transferrin receptor (sTfR): biological variations and reference limits. Clin Chem Lab Med. 2002; 39(11):1162-8. DOI: 10.1515/CCLM.2001.183. View

Parker J, Murphy W, Wang D, OBrien S, Parrish C . Canine and feline parvoviruses can use human or feline transferrin receptors to bind, enter, and infect cells. J Virol. 2001; 75(8):3896-902. PMC: 114880. DOI: 10.1128/JVI.75.8.3896-3902.2001. View

Peters C, Zaki S . Role of the endothelium in viral hemorrhagic fevers. Crit Care Med. 2002; 30(5 Suppl):S268-73. DOI: 10.1097/00003246-200205001-00016. View

Daniels T, Delgado T, Rodriguez J, Helguera G, Penichet M . The transferrin receptor part I: Biology and targeting with cytotoxic antibodies for the treatment of cancer. Clin Immunol. 2006; 121(2):144-58. DOI: 10.1016/j.clim.2006.06.010. View

Borio L, Inglesby T, Peters C, Schmaljohn A, Hughes J, Jahrling P . Hemorrhagic fever viruses as biological weapons: medical and public health management. JAMA. 2002; 287(18):2391-405. DOI: 10.1001/jama.287.18.2391. View

10.

Ross S, Schofield J, Farr C, Bucan M . Mouse transferrin receptor 1 is the cell entry receptor for mouse mammary tumor virus. Proc Natl Acad Sci U S A. 2002; 99(19):12386-90. PMC: 129454. DOI: 10.1073/pnas.192360099. View

11.

Kasvosve I, Delanghe J . Total iron binding capacity and transferrin concentration in the assessment of iron status. Clin Chem Lab Med. 2002; 40(10):1014-8. DOI: 10.1515/CCLM.2002.176. View

12.

Templeton D, Liu Y . Genetic regulation of cell function in response to iron overload or chelation. Biochim Biophys Acta. 2003; 1619(2):113-24. DOI: 10.1016/s0304-4165(02)00497-x. View

13.

Charrel R, de Lamballerie X . Arenaviruses other than Lassa virus. Antiviral Res. 2003; 57(1-2):89-100. DOI: 10.1016/s0166-3542(02)00202-4. View

14.

Li W, Moore M, Vasilieva N, Sui J, Wong S, Berne M . Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426(6965):450-4. PMC: 7095016. DOI: 10.1038/nature02145. View

15.

Wong S, Li W, Moore M, Choe H, Farzan M . A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem. 2003; 279(5):3197-201. PMC: 7982343. DOI: 10.1074/jbc.C300520200. View

16.

Ward J, Kushner J, Kaplan J . Regulation of HeLa cell transferrin receptors. J Biol Chem. 1982; 257(17):10317-23. View

17.

Soda R, Tavassoli M . Liver endothelium and not hepatocytes or Kupffer cells have transferrin receptors. Blood. 1984; 63(2):270-6. View

18.

Mattia E, Rao K, Shapiro D, SUSSMAN H, Klausner R . Biosynthetic regulation of the human transferrin receptor by desferrioxamine in K562 cells. J Biol Chem. 1984; 259(5):2689-92. View

19.

Jefferies W, Brandon M, Hunt S, Williams A, Gatter K, Mason D . Transferrin receptor on endothelium of brain capillaries. Nature. 1984; 312(5990):162-3. DOI: 10.1038/312162a0. View

20.

Buchmeier M, Southern P, Parekh B, Wooddell M, Oldstone M . Site-specific antibodies define a cleavage site conserved among arenavirus GP-C glycoproteins. J Virol. 1987; 61(4):982-5. PMC: 254053. DOI: 10.1128/JVI.61.4.982-985.1987. View