Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients

Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-cir...

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Autores: Vasilijevic, Jasmina, Zamarreño, Noelia, Oliveros, Juan Carlos, Rodriguez-Frandsen, Ariel, Gómez, Guillermo, Rodriguez, Guadalupe, Pérez-Ruiz, Mercedes, Rey, Sonia, Barba, Isabel, Pozo Sanchez, Francisco, Casas Flecha, Inmaculada, Nieto, Amelia, Falcon, Ana
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6718
Acceso en línea:http://hdl.handle.net/20.500.12105/6718
Access Level:acceso abierto
Palabra clave:Adolescent
Adult
Animals
Child
Child, Preschool
Female
Genome, Viral
Humans
Influenza A Virus, H1N1 Subtype
Influenza A Virus, H5N1 Subtype
Influenza, Human
Male
Mice
Middle Aged
Orthomyxoviridae Infections
Virulence
Virus Replication
Young Adult
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/6718
network_acronym_str ES
network_name_str España
repository_id_str
spelling Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patientsVasilijevic, JasminaZamarreño, NoeliaOliveros, Juan CarlosRodriguez-Frandsen, ArielGómez, GuillermoRodriguez, GuadalupePérez-Ruiz, MercedesRey, SoniaBarba, IsabelPozo Sanchez, FranciscoCasas Flecha, InmaculadaNieto, AmeliaFalcon, AnaAdolescentAdultAnimalsChildChild, PreschoolFemaleGenome, ViralHumansInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H5N1 SubtypeInfluenza, HumanMaleMiceMiddle AgedOrthomyxoviridae InfectionsVirulenceVirus ReplicationYoung AdultInfluenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-circulate with pandemic or epidemic viruses. Looking for potential virulence factors, we have identified a polymerase PA D529N mutation detected in a fatal IAV case, whose introduction into two different recombinant virus backbones, led to reduced defective viral genomes (DVGs) production. This mutation conferred low induction of antiviral response in infected cells and increased pathogenesis in mice. To analyze the association between low DVGs production and pathogenesis in humans, we performed a genomic analysis of viruses isolated from a cohort of previously healthy individuals who suffered highly severe IAV infection requiring admission to Intensive Care Unit and patients with fatal outcome who additionally showed underlying medical conditions. These viruses were compared with those isolated from a cohort of mild IAV patients. Viruses with fewer DVGs accumulation were observed in patients with highly severe/fatal outcome than in those with mild disease, suggesting that low DVGs abundance constitutes a new virulence pathogenic marker in humans.Public Library of Science (PLOS)Ministerio de Economía y Competitividad (España)20182018-11-2320172017-10-1220172017-10-12journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/6718reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES BFU2011-26175 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/67182026-06-12T12:43:37Z
dc.title.none.fl_str_mv Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients
title Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients
spellingShingle Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients
Vasilijevic, Jasmina
Adolescent
Adult
Animals
Child
Child, Preschool
Female
Genome, Viral
Humans
Influenza A Virus, H1N1 Subtype
Influenza A Virus, H5N1 Subtype
Influenza, Human
Male
Mice
Middle Aged
Orthomyxoviridae Infections
Virulence
Virus Replication
Young Adult
title_short Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients
title_full Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients
title_fullStr Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients
title_full_unstemmed Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients
title_sort Reduced accumulation of defective viral genomes contributes to severe outcome in influenza virus infected patients
dc.creator.none.fl_str_mv Vasilijevic, Jasmina
Zamarreño, Noelia
Oliveros, Juan Carlos
Rodriguez-Frandsen, Ariel
Gómez, Guillermo
Rodriguez, Guadalupe
Pérez-Ruiz, Mercedes
Rey, Sonia
Barba, Isabel
Pozo Sanchez, Francisco
Casas Flecha, Inmaculada
Nieto, Amelia
Falcon, Ana
author Vasilijevic, Jasmina
author_facet Vasilijevic, Jasmina
Zamarreño, Noelia
Oliveros, Juan Carlos
Rodriguez-Frandsen, Ariel
Gómez, Guillermo
Rodriguez, Guadalupe
Pérez-Ruiz, Mercedes
Rey, Sonia
Barba, Isabel
Pozo Sanchez, Francisco
Casas Flecha, Inmaculada
Nieto, Amelia
Falcon, Ana
author_role author
author2 Zamarreño, Noelia
Oliveros, Juan Carlos
Rodriguez-Frandsen, Ariel
Gómez, Guillermo
Rodriguez, Guadalupe
Pérez-Ruiz, Mercedes
Rey, Sonia
Barba, Isabel
Pozo Sanchez, Francisco
Casas Flecha, Inmaculada
Nieto, Amelia
Falcon, Ana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
dc.subject.none.fl_str_mv Adolescent
Adult
Animals
Child
Child, Preschool
Female
Genome, Viral
Humans
Influenza A Virus, H1N1 Subtype
Influenza A Virus, H5N1 Subtype
Influenza, Human
Male
Mice
Middle Aged
Orthomyxoviridae Infections
Virulence
Virus Replication
Young Adult
topic Adolescent
Adult
Animals
Child
Child, Preschool
Female
Genome, Viral
Humans
Influenza A Virus, H1N1 Subtype
Influenza A Virus, H5N1 Subtype
Influenza, Human
Male
Mice
Middle Aged
Orthomyxoviridae Infections
Virulence
Virus Replication
Young Adult
description Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-circulate with pandemic or epidemic viruses. Looking for potential virulence factors, we have identified a polymerase PA D529N mutation detected in a fatal IAV case, whose introduction into two different recombinant virus backbones, led to reduced defective viral genomes (DVGs) production. This mutation conferred low induction of antiviral response in infected cells and increased pathogenesis in mice. To analyze the association between low DVGs production and pathogenesis in humans, we performed a genomic analysis of viruses isolated from a cohort of previously healthy individuals who suffered highly severe IAV infection requiring admission to Intensive Care Unit and patients with fatal outcome who additionally showed underlying medical conditions. These viruses were compared with those isolated from a cohort of mild IAV patients. Viruses with fewer DVGs accumulation were observed in patients with highly severe/fatal outcome than in those with mild disease, suggesting that low DVGs abundance constitutes a new virulence pathogenic marker in humans.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-10-12
2017
2017-10-12
2018
2018-11-23
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/6718
url http://hdl.handle.net/20.500.12105/6718
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES BFU2011-26175 Not available
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLOS)
publisher.none.fl_str_mv Public Library of Science (PLOS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,30478

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