Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity
Oseltamivir is a common therapy against influenza A virus (IAV) infections. The acquisition of oseltamivir resistance (OR) mutations, such as H275Y, hampers viral fitness. However, OR H1N1 viruses have demonstrated the ability to spread throughout different populations. The objective of this work wa...
| Autores: | , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:252793 |
| Acceso en línea: | https://ddd.uab.cat/record/252793 https://dx.doi.org/urn:doi:10.3390/v12080794 |
| Access Level: | acceso abierto |
| Palabra clave: | Influenza Immunopathology Pneumonia Ph1n1 Resistance Oseltamivir |
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Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus PathogenicityVidaña, Beatriz|||0000-0003-1724-1006Martinez Orellana, Pamela Analia|||0000-0002-2025-9445Martorell Montserrat, Jaume|||0000-0001-9031-0042Baratelli, Massimiliano|||0000-0001-5990-4045Martínez Martínez, Jorge|||0000-0001-5246-7276Migura-Garcia, Lourdes|||0000-0003-2935-928XCórdoba, LorenaPérez-Maíllo, MónicaCasas, Inmaculada|||0000-0003-1840-1198Pozo, Francisco|||0000-0003-1828-733XFraile, Lorenzo|||0000-0002-8980-5862Majó i Masferrer, Natàlia|||0000-0003-0189-9751Montoya, Maria|||0000-0002-5703-7360InfluenzaImmunopathologyPneumoniaPh1n1ResistanceOseltamivirOseltamivir is a common therapy against influenza A virus (IAV) infections. The acquisition of oseltamivir resistance (OR) mutations, such as H275Y, hampers viral fitness. However, OR H1N1 viruses have demonstrated the ability to spread throughout different populations. The objective of this work was to compare the fitness of two strains of OR (R6 and R7) containing the H275Y mutation, and a wild-type (F) pandemic influenza A (H1N1) 2009 (pdm09) virus both in vitro and in vivo in mice and to select one OR strain for a comparison with F in ferrets. R6 showed faster replication and pathogenicity than R7 in vitro and in mice. Subsequently, R6 was selected for the fitness comparison with the F strain in ferrets. Ferrets infected with the F virus showed more severe clinical signs, histopathological lung lesions, and viral quantification when compared to OR R6-infected animals. More importantly, differential viral kinetics correlated with differential pro-inflammatory host immune responses in the lungs of infected ferrets, where OR-infected animals developed a protective higher expression of type I IFN and Retinoid acid Inducible Gene I (RIG-I) genes early after infection, resulting in the development of milder disease. These results suggest the presence of early specific viral-host immune interactions relevant in the development of influenza-associated lung pathology. 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/252793https://dx.doi.org/urn:doi:10.3390/v12080794reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 GR09/0023Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 GR09/0040Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 GR09/0039open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2527932026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity |
| title |
Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity |
| spellingShingle |
Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity Vidaña, Beatriz|||0000-0003-1724-1006 Influenza Immunopathology Pneumonia Ph1n1 Resistance Oseltamivir |
| title_short |
Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity |
| title_full |
Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity |
| title_fullStr |
Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity |
| title_full_unstemmed |
Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity |
| title_sort |
Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity |
| dc.creator.none.fl_str_mv |
Vidaña, Beatriz|||0000-0003-1724-1006 Martinez Orellana, Pamela Analia|||0000-0002-2025-9445 Martorell Montserrat, Jaume|||0000-0001-9031-0042 Baratelli, Massimiliano|||0000-0001-5990-4045 Martínez Martínez, Jorge|||0000-0001-5246-7276 Migura-Garcia, Lourdes|||0000-0003-2935-928X Córdoba, Lorena Pérez-Maíllo, Mónica Casas, Inmaculada|||0000-0003-1840-1198 Pozo, Francisco|||0000-0003-1828-733X Fraile, Lorenzo|||0000-0002-8980-5862 Majó i Masferrer, Natàlia|||0000-0003-0189-9751 Montoya, Maria|||0000-0002-5703-7360 |
| author |
Vidaña, Beatriz|||0000-0003-1724-1006 |
| author_facet |
Vidaña, Beatriz|||0000-0003-1724-1006 Martinez Orellana, Pamela Analia|||0000-0002-2025-9445 Martorell Montserrat, Jaume|||0000-0001-9031-0042 Baratelli, Massimiliano|||0000-0001-5990-4045 Martínez Martínez, Jorge|||0000-0001-5246-7276 Migura-Garcia, Lourdes|||0000-0003-2935-928X Córdoba, Lorena Pérez-Maíllo, Mónica Casas, Inmaculada|||0000-0003-1840-1198 Pozo, Francisco|||0000-0003-1828-733X Fraile, Lorenzo|||0000-0002-8980-5862 Majó i Masferrer, Natàlia|||0000-0003-0189-9751 Montoya, Maria|||0000-0002-5703-7360 |
| author_role |
author |
| author2 |
Martinez Orellana, Pamela Analia|||0000-0002-2025-9445 Martorell Montserrat, Jaume|||0000-0001-9031-0042 Baratelli, Massimiliano|||0000-0001-5990-4045 Martínez Martínez, Jorge|||0000-0001-5246-7276 Migura-Garcia, Lourdes|||0000-0003-2935-928X Córdoba, Lorena Pérez-Maíllo, Mónica Casas, Inmaculada|||0000-0003-1840-1198 Pozo, Francisco|||0000-0003-1828-733X Fraile, Lorenzo|||0000-0002-8980-5862 Majó i Masferrer, Natàlia|||0000-0003-0189-9751 Montoya, Maria|||0000-0002-5703-7360 |
| author2_role |
author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Influenza Immunopathology Pneumonia Ph1n1 Resistance Oseltamivir |
| topic |
Influenza Immunopathology Pneumonia Ph1n1 Resistance Oseltamivir |
| description |
Oseltamivir is a common therapy against influenza A virus (IAV) infections. The acquisition of oseltamivir resistance (OR) mutations, such as H275Y, hampers viral fitness. However, OR H1N1 viruses have demonstrated the ability to spread throughout different populations. The objective of this work was to compare the fitness of two strains of OR (R6 and R7) containing the H275Y mutation, and a wild-type (F) pandemic influenza A (H1N1) 2009 (pdm09) virus both in vitro and in vivo in mice and to select one OR strain for a comparison with F in ferrets. R6 showed faster replication and pathogenicity than R7 in vitro and in mice. Subsequently, R6 was selected for the fitness comparison with the F strain in ferrets. Ferrets infected with the F virus showed more severe clinical signs, histopathological lung lesions, and viral quantification when compared to OR R6-infected animals. More importantly, differential viral kinetics correlated with differential pro-inflammatory host immune responses in the lungs of infected ferrets, where OR-infected animals developed a protective higher expression of type I IFN and Retinoid acid Inducible Gene I (RIG-I) genes early after infection, resulting in the development of milder disease. These results suggest the presence of early specific viral-host immune interactions relevant in the development of influenza-associated lung pathology. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2 2020-01-01 2020 2020-01-01 |
| dc.type.none.fl_str_mv |
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 |
https://ddd.uab.cat/record/252793 https://dx.doi.org/urn:doi:10.3390/v12080794 |
| url |
https://ddd.uab.cat/record/252793 https://dx.doi.org/urn:doi:10.3390/v12080794 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 GR09/0023 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 GR09/0040 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 GR09/0039 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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