title: Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Genetics and New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA.
authors.forename: Sheli R
authors.initials: SR
authors.lastname: Radoshitzky
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
authors.forename: César G
authors.initials: CG
authors.lastname: Albariño
authors.forename: Dan P
authors.initials: DP
authors.lastname: Nguyen
authors.forename: Jorge
authors.initials: J
authors.lastname: Salazar-Bravo
authors.forename: Tatyana
authors.initials: T
authors.lastname: Dorfman
authors.forename: Amy S
authors.initials: AS
authors.lastname: Lee
authors.forename: Enxiu
authors.initials: E
authors.lastname: Wang
authors.forename: Susan R
authors.initials: SR
authors.lastname: Ross
authors.forename: Hyeryun
authors.initials: H
authors.lastname: Choe
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001117:Arenaviridae Infections / Q000235:genetics / Q000378:metabolism / Q000635:transmission*; D006477:Arenaviruses, New World / Q000502:physiology*; D001665:Binding Sites; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011990:Receptors, Transferrin / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D011990:Receptors, Transferrin; D014443:Tyrosine; D020559:Monomeric GTP-Binding Proteins