title: Genome-Wide Screening of Retroviral Envelope Genes in the Nine-Banded Armadillo (Dasypus novemcinctus, Xenarthra) Reveals an Unfixed Chimeric Endogenous Betaretrovirus Using the ASCT2 Receptor.
abstract: Retroviruses enter host cells through the interaction of their envelope (Env) protein with a cell surface receptor, which triggers the fusion of viral and cellular membranes. The sodium-dependent neutral amino acid transporter ASCT2 is the common receptor of the large RD114 retrovirus interference group, whose members display frequent env recombination events. Germ line retrovirus infections have led to numerous inherited endogenous retroviruses (ERVs) in vertebrate genomes, which provide useful insights into the coevolutionary history of retroviruses and their hosts. Rare ERV-derived genes display conserved viral functions, as illustrated by the fusogenic syncytin env genes involved in placentation. Here, we searched for functional env genes in the nine-banded armadillo (Dasypus novemcinctus) genome and identified dasy-env1.1, which clusters with RD114 interference group env genes and with two syncytin genes sharing ASCT2 receptor usage. Using ex vivo pseudotyping and cell-cell fusion assays, we demonstrated that the Dasy-Env1.1 protein is fusogenic and can use both human and armadillo ASCT2s as receptors. This gammaretroviral env gene belongs to a provirus with betaretrovirus-like features, suggesting acquisition through recombination. Provirus insertion was found in several Dasypus species, where it has not reached fixation, whereas related family members integrated before diversification of the genus Dasypus >12 million years ago (Mya). This newly described ERV lineage is potentially useful as a population genetic marker. Our results extend the usage of ASCT2 as a retrovirus receptor to the mammalian clade Xenarthra and suggest that the acquisition of an ASCT2-interacting env gene is a major selective force driving the emergence of numerous chimeric viruses in vertebrates.
  
  
  
  Retroviral infection is initiated by the binding of the viral envelope glycoprotein to a host cell receptor(s), triggering membrane fusion. Ancient germ line infections have generated numerous endogenous retroviruses (ERVs) in nearly all vertebrate genomes. Here, we report a previously uncharacterized ERV lineage from the genome of a xenarthran species, the nine-banded armadillo (Dasypus novemcinctus). It entered the Dasypus genus >12 Mya, with one element being inserted more recently in some Dasypus species, where it could serve as a useful marker for population genetics. This element exhibits an env gene, acquired by recombination events, with conserved viral fusogenic properties through binding to ASCT2, a receptor used by a wide range of recombinant retroviruses infecting other vertebrate orders. This specifies the ASCT2 transporter as a successful receptor for ERV endogenization and suggests that ASCT2-binding env acquisition events have favored the emergence of numerous chimeric viruses in a wide range of species.
authors.affiliation: Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Unité Mixte de Recherche 9196, Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, and Université Paris-Sud, Orsay, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Malicorne
authors.affiliation: Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Unité Mixte de Recherche 9196, Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, and Université Paris-Sud, Orsay, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Vernochet
authors.affiliation: Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Unité Mixte de Recherche 9196, Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, and Université Paris-Sud, Orsay, France Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cornelis
authors.affiliation: ZooParc de Beauval and Beauval Nature, Saint Aignan, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Mulot
authors.affiliation: Institut des Sciences de l'Evolution, UMR 5554, CNRS, IRD, EPHE, Université de Montpellier, Montpellier, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Delsuc
authors.affiliation: Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Unité Mixte de Recherche 9196, Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, and Université Paris-Sud, Orsay, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Heidmann
authors.affiliation: Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Unité Mixte de Recherche 9196, Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, and Université Paris-Sud, Orsay, France heidmann@igr.fr dupresso@igr.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Heidmann
authors.affiliation: Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Unité Mixte de Recherche 9196, Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, and Université Paris-Sud, Orsay, France heidmann@igr.fr dupresso@igr.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Dupressoir
mesh_terms: D026962:Amino Acid Transport System ASC / Q000378:metabolism*; D000818:Animals; D001135:Armadillos / Q000821:virology*; D030121:Betaretrovirus / Q000235:genetics / Q000302:isolation & purification*; D020077:Endogenous Retroviruses / Q000235:genetics / Q000302:isolation & purification*; D005820:Genetic Testing; D015778:Minor Histocompatibility Antigens / Q000378:metabolism*; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification*; D011991:Receptors, Virus / Q000378:metabolism*; D011995:Recombination, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D026962:Amino Acid Transport System ASC; D015778:Minor Histocompatibility Antigens; D011991:Receptors, Virus; C420506:SLC1A5 protein, human; D014759:Viral Envelope Proteins