Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission

Autores
Bellomo, Carla María; Alonso, Daniel O.; Pérez Sautu, Unai; Prieto, Karla; Kehl, Sebastian Dario; Coelho, Rocío María; Periolo, Natalia; Di Paola, Nicholas; Ferressini Gerpe, Natalia; Kuhn, Jens H.; Sanchez Lockhart, Mariano; Palacios, Gustavo; Martinez, Valeria Paula
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.
Fil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
Fil: Alonso, Daniel O.. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
Fil: Pérez Sautu, Unai. No especifíca;
Fil: Prieto, Karla. No especifíca;
Fil: Kehl, Sebastian Dario. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
Fil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
Fil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Di Paola, Nicholas. No especifíca;
Fil: Ferressini Gerpe, Natalia. No especifíca;
Fil: Kuhn, Jens H.. No especifíca;
Fil: Sanchez Lockhart, Mariano. No especifíca;
Fil: Palacios, Gustavo. No especifíca;
Fil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
Materia
COMPARATIVE GENOMICS
ORTHOHANTAVIRUS
PERSON-TO-PERSON TRANSMISSION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/220138
Acceder
id CONICETDig_26f3f053d130916d3e81ba950f868ecb
oai_identifier_str oai:ri.conicet.gov.ar:11336/220138
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person TransmissionBellomo, Carla MaríaAlonso, Daniel O.Pérez Sautu, UnaiPrieto, KarlaKehl, Sebastian DarioCoelho, Rocío MaríaPeriolo, NataliaDi Paola, NicholasFerressini Gerpe, NataliaKuhn, Jens H.Sanchez Lockhart, MarianoPalacios, GustavoMartinez, Valeria PaulaCOMPARATIVE GENOMICSORTHOHANTAVIRUSPERSON-TO-PERSON TRANSMISSIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.Fil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Alonso, Daniel O.. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Pérez Sautu, Unai. No especifíca;Fil: Prieto, Karla. No especifíca;Fil: Kehl, Sebastian Dario. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Di Paola, Nicholas. No especifíca;Fil: Ferressini Gerpe, Natalia. No especifíca;Fil: Kuhn, Jens H.. No especifíca;Fil: Sanchez Lockhart, Mariano. No especifíca;Fil: Palacios, Gustavo. No especifíca;Fil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaAmerican Society for Microbiology2023-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/220138Bellomo, Carla María; Alonso, Daniel O.; Pérez Sautu, Unai; Prieto, Karla; Kehl, Sebastian Dario; et al.; Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission; American Society for Microbiology; mSphere; 8; 3; 4-2023; 1-142379-5042CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/msphere.00018-23info:eu-repo/semantics/altIdentifier/doi/10.1128/msphere.00018-23info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:07:47Zoai:ri.conicet.gov.ar:11336/220138instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:07:47.708CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
title Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
spellingShingle Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
Bellomo, Carla María
COMPARATIVE GENOMICS
ORTHOHANTAVIRUS
PERSON-TO-PERSON TRANSMISSION
title_short Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
title_full Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
title_fullStr Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
title_full_unstemmed Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
title_sort Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
dc.creator.none.fl_str_mv Bellomo, Carla María
Alonso, Daniel O.
Pérez Sautu, Unai
Prieto, Karla
Kehl, Sebastian Dario
Coelho, Rocío María
Periolo, Natalia
Di Paola, Nicholas
Ferressini Gerpe, Natalia
Kuhn, Jens H.
Sanchez Lockhart, Mariano
Palacios, Gustavo
Martinez, Valeria Paula
author Bellomo, Carla María
author_facet Bellomo, Carla María
Alonso, Daniel O.
Pérez Sautu, Unai
Prieto, Karla
Kehl, Sebastian Dario
Coelho, Rocío María
Periolo, Natalia
Di Paola, Nicholas
Ferressini Gerpe, Natalia
Kuhn, Jens H.
Sanchez Lockhart, Mariano
Palacios, Gustavo
Martinez, Valeria Paula
author_role author
author2 Alonso, Daniel O.
Pérez Sautu, Unai
Prieto, Karla
Kehl, Sebastian Dario
Coelho, Rocío María
Periolo, Natalia
Di Paola, Nicholas
Ferressini Gerpe, Natalia
Kuhn, Jens H.
Sanchez Lockhart, Mariano
Palacios, Gustavo
Martinez, Valeria Paula
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COMPARATIVE GENOMICS
ORTHOHANTAVIRUS
PERSON-TO-PERSON TRANSMISSION
topic COMPARATIVE GENOMICS
ORTHOHANTAVIRUS
PERSON-TO-PERSON TRANSMISSION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.
Fil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
Fil: Alonso, Daniel O.. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
Fil: Pérez Sautu, Unai. No especifíca;
Fil: Prieto, Karla. No especifíca;
Fil: Kehl, Sebastian Dario. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
Fil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
Fil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Di Paola, Nicholas. No especifíca;
Fil: Ferressini Gerpe, Natalia. No especifíca;
Fil: Kuhn, Jens H.. No especifíca;
Fil: Sanchez Lockhart, Mariano. No especifíca;
Fil: Palacios, Gustavo. No especifíca;
Fil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina
description We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.
publishDate 2023
dc.date.none.fl_str_mv 2023-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/220138
Bellomo, Carla María; Alonso, Daniel O.; Pérez Sautu, Unai; Prieto, Karla; Kehl, Sebastian Dario; et al.; Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission; American Society for Microbiology; mSphere; 8; 3; 4-2023; 1-14
2379-5042
CONICET Digital
CONICET
url http://hdl.handle.net/11336/220138
identifier_str_mv Bellomo, Carla María; Alonso, Daniel O.; Pérez Sautu, Unai; Prieto, Karla; Kehl, Sebastian Dario; et al.; Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission; American Society for Microbiology; mSphere; 8; 3; 4-2023; 1-14
2379-5042
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/msphere.00018-23
info:eu-repo/semantics/altIdentifier/doi/10.1128/msphere.00018-23
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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