Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome

Autores
Iglesias, Ayelén Aluminé; Periolo, Natalia; Bellomo, Carla María; Lewis, Lorena Cecilia; Olivera, Camila Paula; Rosario Anselmo, Constanza; García, Marina; Coelho, Rocío María; Alonso, Daniel Oscar; Dighero Kemp, Bonnie; Sharma, Heema; Kuhn, Jens H.; Di Paola, Nicholas; Sanchez Lockhart, Mariano; Palacios, Gustavo; Schierloh, Luis Pablo; Martinez, Valeria Paula
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction. Although an exacerbated immune response is thought to be implicated in pathogenesis, clear evidence is still elusive. As orthohantaviruses are not cytopathic CD8+ T cells are believed to be the central players involved in pathogenesis. Methods: Serum and blood samples from Argentinean HPS patients were collected from 2014 to 2019. Routine white blood cell analyses, quantification and characterization of T-cell phenotypic profile, viral load, neutralizing antibody response and quantification of inflammatory mediators were performed. Findings: High numbers of activated CD4+ and CD8+ T cells were found in all HPS cases independently of disease severity. We found increased levels of some proinflammatory mediators during the acute phase of illness. Nonetheless, viral RNA remained high, showing a delay in clearance from blood up to late convalescence, when titers of neutralizing antibodies reached a high level. Interpretation: The high activated phenotypic profile of T cells seems to be unable to resolve infection during the acute and early convalescent phases, and it was not associated with the severity of the disease. Thus, at least part of the activated T cells could be induced by the dysregulated inflammatory response in an unspecific manner. Viral clearance seems to have been more related to high titers of neutralizing antibodies than to the T-cell response. Funding: This work was supported mainly by the Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos Malbrán”. Further details of fundings sources is included in the appendix.
Fil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Fil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Fil: Lewis, Lorena Cecilia. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; Argentina
Fil: Olivera, Camila Paula. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; Argentina
Fil: Rosario Anselmo, Constanza. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; Argentina
Fil: García, Marina. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Fil: Alonso, Daniel Oscar. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Fil: Dighero Kemp, Bonnie. National Institute Of Allergy And Infectious Diseases; Estados Unidos
Fil: Sharma, Heema. National Institute Of Allergy And Infectious Diseases; Estados Unidos
Fil: Kuhn, Jens H.. National Institute Of Allergy And Infectious Diseases; Estados Unidos
Fil: Di Paola, Nicholas. Center For Genome Sciences, U.s. Army Medical Research; Estados Unidos
Fil: Sanchez Lockhart, Mariano. Center For Genome Sciences, U.s. Army Medical Research; Estados Unidos
Fil: Palacios, Gustavo. Center For Genome Sciences, U.s. Army Medical Research; Estados Unidos
Fil: Schierloh, Luis Pablo. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; Argentina
Fil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Materia
ANDES VIRUS
HANTAVIRIDAE
HANTAVIRUS PULMONARY SYNDROME
ORTHOHANTAVIRUS
T CELLS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/213721
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/213721
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndromeIglesias, Ayelén AluminéPeriolo, NataliaBellomo, Carla MaríaLewis, Lorena CeciliaOlivera, Camila PaulaRosario Anselmo, ConstanzaGarcía, MarinaCoelho, Rocío MaríaAlonso, Daniel OscarDighero Kemp, BonnieSharma, HeemaKuhn, Jens H.Di Paola, NicholasSanchez Lockhart, MarianoPalacios, GustavoSchierloh, Luis PabloMartinez, Valeria PaulaANDES VIRUSHANTAVIRIDAEHANTAVIRUS PULMONARY SYNDROMEORTHOHANTAVIRUST CELLShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction. Although an exacerbated immune response is thought to be implicated in pathogenesis, clear evidence is still elusive. As orthohantaviruses are not cytopathic CD8+ T cells are believed to be the central players involved in pathogenesis. Methods: Serum and blood samples from Argentinean HPS patients were collected from 2014 to 2019. Routine white blood cell analyses, quantification and characterization of T-cell phenotypic profile, viral load, neutralizing antibody response and quantification of inflammatory mediators were performed. Findings: High numbers of activated CD4+ and CD8+ T cells were found in all HPS cases independently of disease severity. We found increased levels of some proinflammatory mediators during the acute phase of illness. Nonetheless, viral RNA remained high, showing a delay in clearance from blood up to late convalescence, when titers of neutralizing antibodies reached a high level. Interpretation: The high activated phenotypic profile of T cells seems to be unable to resolve infection during the acute and early convalescent phases, and it was not associated with the severity of the disease. Thus, at least part of the activated T cells could be induced by the dysregulated inflammatory response in an unspecific manner. Viral clearance seems to have been more related to high titers of neutralizing antibodies than to the T-cell response. Funding: This work was supported mainly by the Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos Malbrán”. Further details of fundings sources is included in the appendix.Fil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Lewis, Lorena Cecilia. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; ArgentinaFil: Olivera, Camila Paula. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; ArgentinaFil: Rosario Anselmo, Constanza. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; ArgentinaFil: García, Marina. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Alonso, Daniel Oscar. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Dighero Kemp, Bonnie. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Sharma, Heema. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Kuhn, Jens H.. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Di Paola, Nicholas. Center For Genome Sciences, U.s. Army Medical Research; Estados UnidosFil: Sanchez Lockhart, Mariano. Center For Genome Sciences, U.s. Army Medical Research; Estados UnidosFil: Palacios, Gustavo. Center For Genome Sciences, U.s. Army Medical Research; Estados UnidosFil: Schierloh, Luis Pablo. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaElsevier2022-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/213721Iglesias, Ayelén Aluminé; Periolo, Natalia; Bellomo, Carla María; Lewis, Lorena Cecilia; Olivera, Camila Paula; et al.; Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome; Elsevier; eBioMedicine; 75; 1-2022; 1-122352-3964CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2352396421005594info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ebiom.2021.103765info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:37:47Zoai:ri.conicet.gov.ar:11336/213721instacron: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 09:37:48.143CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome
title Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome
spellingShingle Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome
Iglesias, Ayelén Aluminé
ANDES VIRUS
HANTAVIRIDAE
HANTAVIRUS PULMONARY SYNDROME
ORTHOHANTAVIRUS
T CELLS
title_short Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome
title_full Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome
title_fullStr Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome
title_full_unstemmed Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome
title_sort Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome
dc.creator.none.fl_str_mv Iglesias, Ayelén Aluminé
Periolo, Natalia
Bellomo, Carla María
Lewis, Lorena Cecilia
Olivera, Camila Paula
Rosario Anselmo, Constanza
García, Marina
Coelho, Rocío María
Alonso, Daniel Oscar
Dighero Kemp, Bonnie
Sharma, Heema
Kuhn, Jens H.
Di Paola, Nicholas
Sanchez Lockhart, Mariano
Palacios, Gustavo
Schierloh, Luis Pablo
Martinez, Valeria Paula
author Iglesias, Ayelén Aluminé
author_facet Iglesias, Ayelén Aluminé
Periolo, Natalia
Bellomo, Carla María
Lewis, Lorena Cecilia
Olivera, Camila Paula
Rosario Anselmo, Constanza
García, Marina
Coelho, Rocío María
Alonso, Daniel Oscar
Dighero Kemp, Bonnie
Sharma, Heema
Kuhn, Jens H.
Di Paola, Nicholas
Sanchez Lockhart, Mariano
Palacios, Gustavo
Schierloh, Luis Pablo
Martinez, Valeria Paula
author_role author
author2 Periolo, Natalia
Bellomo, Carla María
Lewis, Lorena Cecilia
Olivera, Camila Paula
Rosario Anselmo, Constanza
García, Marina
Coelho, Rocío María
Alonso, Daniel Oscar
Dighero Kemp, Bonnie
Sharma, Heema
Kuhn, Jens H.
Di Paola, Nicholas
Sanchez Lockhart, Mariano
Palacios, Gustavo
Schierloh, Luis Pablo
Martinez, Valeria Paula
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANDES VIRUS
HANTAVIRIDAE
HANTAVIRUS PULMONARY SYNDROME
ORTHOHANTAVIRUS
T CELLS
topic ANDES VIRUS
HANTAVIRIDAE
HANTAVIRUS PULMONARY SYNDROME
ORTHOHANTAVIRUS
T CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction. Although an exacerbated immune response is thought to be implicated in pathogenesis, clear evidence is still elusive. As orthohantaviruses are not cytopathic CD8+ T cells are believed to be the central players involved in pathogenesis. Methods: Serum and blood samples from Argentinean HPS patients were collected from 2014 to 2019. Routine white blood cell analyses, quantification and characterization of T-cell phenotypic profile, viral load, neutralizing antibody response and quantification of inflammatory mediators were performed. Findings: High numbers of activated CD4+ and CD8+ T cells were found in all HPS cases independently of disease severity. We found increased levels of some proinflammatory mediators during the acute phase of illness. Nonetheless, viral RNA remained high, showing a delay in clearance from blood up to late convalescence, when titers of neutralizing antibodies reached a high level. Interpretation: The high activated phenotypic profile of T cells seems to be unable to resolve infection during the acute and early convalescent phases, and it was not associated with the severity of the disease. Thus, at least part of the activated T cells could be induced by the dysregulated inflammatory response in an unspecific manner. Viral clearance seems to have been more related to high titers of neutralizing antibodies than to the T-cell response. Funding: This work was supported mainly by the Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos Malbrán”. Further details of fundings sources is included in the appendix.
Fil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Fil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Fil: Lewis, Lorena Cecilia. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; Argentina
Fil: Olivera, Camila Paula. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; Argentina
Fil: Rosario Anselmo, Constanza. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; Argentina
Fil: García, Marina. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Fil: Alonso, Daniel Oscar. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
Fil: Dighero Kemp, Bonnie. National Institute Of Allergy And Infectious Diseases; Estados Unidos
Fil: Sharma, Heema. National Institute Of Allergy And Infectious Diseases; Estados Unidos
Fil: Kuhn, Jens H.. National Institute Of Allergy And Infectious Diseases; Estados Unidos
Fil: Di Paola, Nicholas. Center For Genome Sciences, U.s. Army Medical Research; Estados Unidos
Fil: Sanchez Lockhart, Mariano. Center For Genome Sciences, U.s. Army Medical Research; Estados Unidos
Fil: Palacios, Gustavo. Center For Genome Sciences, U.s. Army Medical Research; Estados Unidos
Fil: Schierloh, Luis Pablo. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; Argentina
Fil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina
description Background: The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction. Although an exacerbated immune response is thought to be implicated in pathogenesis, clear evidence is still elusive. As orthohantaviruses are not cytopathic CD8+ T cells are believed to be the central players involved in pathogenesis. Methods: Serum and blood samples from Argentinean HPS patients were collected from 2014 to 2019. Routine white blood cell analyses, quantification and characterization of T-cell phenotypic profile, viral load, neutralizing antibody response and quantification of inflammatory mediators were performed. Findings: High numbers of activated CD4+ and CD8+ T cells were found in all HPS cases independently of disease severity. We found increased levels of some proinflammatory mediators during the acute phase of illness. Nonetheless, viral RNA remained high, showing a delay in clearance from blood up to late convalescence, when titers of neutralizing antibodies reached a high level. Interpretation: The high activated phenotypic profile of T cells seems to be unable to resolve infection during the acute and early convalescent phases, and it was not associated with the severity of the disease. Thus, at least part of the activated T cells could be induced by the dysregulated inflammatory response in an unspecific manner. Viral clearance seems to have been more related to high titers of neutralizing antibodies than to the T-cell response. Funding: This work was supported mainly by the Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos Malbrán”. Further details of fundings sources is included in the appendix.
publishDate 2022
dc.date.none.fl_str_mv 2022-01
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/11336/213721
Iglesias, Ayelén Aluminé; Periolo, Natalia; Bellomo, Carla María; Lewis, Lorena Cecilia; Olivera, Camila Paula; et al.; Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome; Elsevier; eBioMedicine; 75; 1-2022; 1-12
2352-3964
CONICET Digital
CONICET
url http://hdl.handle.net/11336/213721
identifier_str_mv Iglesias, Ayelén Aluminé; Periolo, Natalia; Bellomo, Carla María; Lewis, Lorena Cecilia; Olivera, Camila Paula; et al.; Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome; Elsevier; eBioMedicine; 75; 1-2022; 1-12
2352-3964
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ebiom.2021.103765
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
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application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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