Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses

Sheli R. Radoshitzky, Jens H. Kuhn, Christina F. Spiropoulou, César G. Albariño, Dan P. Nguyen, Jorge Salazar-Bravo, Tatyana Dorfman, Amy S. Lee, Enxiu Wang, Susan R. Ross, Hyeryun Choe, Michael Farzan

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


Transferrin receptor 1 (TfR1) is a cellular receptor for the New World hemorrhagic fever arenaviruses Machupo (MACV), Junín (JUNV), and Guanarito (GTOV). Each of these viruses is specifically adapted to a distinct rodent host species, but all cause human disease. Here we compare the ability of these viruses to use various mammalian transferrin receptor 1 (TfR1) orthologs, including those of the South American rodents that serve as reservoirs for MACV, JUNV, and GTOV (Calomys callosus, Calomys musculinus, and Zygodontomys brevicauda, respectively). Retroviruses pseudotyped with MACV and JUNV but not GTOV glycoproteins (GPs) efficiently used C. callosus TfR1, whereas only JUNV GP could use C. musculinus TfR1. All three viruses efficiently used Z. brevicauda TfR1. TfR1 orthologs from related rodents, including house mouse (Mus musculus) and rat (Rattus norvegicus), did not support entry of these viruses. In contrast, these viruses efficiently used human and domestic cat TfR1 orthologs. We further show that a local region of the human TfR1 apical domain, including tyrosine 211, determined the efficiency with which MACV, JUNV, and GTOV used various TfR1 orthologs. Our data show that these New World arenaviruses are specifically adapted to the TfR1 orthologs of their respective rodent hosts and identify key commonalities between these orthologs and human TfR1 necessary for efficient transmission of these viruses to humans.

Original languageEnglish
Pages (from-to)2664-2669
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 19 2008


  • Calomys
  • Junín virus
  • Machupo virus
  • Transferrin receptor 1


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