Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling

Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by Junín virus (JUNV), a member of the arenaviridae family. Although a recently introduced live attenuated vaccine has proven to be effective, AHF remains a potentially lethal infection. Like in other viral hemorrhagic fevers (VH...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Pozner, Roberto G., Ure, Agustín Enrique, Jaquenod De Giusti, Carolina, D'Atri, Lina P., Italiano, Joseph E., Torres, Oscar, Romanowski, Víctor, Schattner, Mirta, Gómez, Ricardo Martín
Formato: Articulo
Lenguaje:Inglés
Publicado: 2010
Materias:
Bioquímica
Fiebre Hemorrágica Americana
Arenaviridae
Trombocitopenia
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/29442
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000847
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-29442
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
Fiebre Hemorrágica Americana
Arenaviridae
Trombocitopenia
spellingShingle Bioquímica
Fiebre Hemorrágica Americana
Arenaviridae
Trombocitopenia
Pozner, Roberto G.
Ure, Agustín Enrique
Jaquenod De Giusti, Carolina
D'Atri, Lina P.
Italiano, Joseph E.
Torres, Oscar
Romanowski, Víctor
Schattner, Mirta
Gómez, Ricardo Martín
Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling
topic_facet Bioquímica
Fiebre Hemorrágica Americana
Arenaviridae
Trombocitopenia
description Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by Junín virus (JUNV), a member of the arenaviridae family. Although a recently introduced live attenuated vaccine has proven to be effective, AHF remains a potentially lethal infection. Like in other viral hemorrhagic fevers (VHF), AHF patients present with fever and hemorrhagic complications. Although the causes of the bleeding are poorly understood, impaired hemostasis, endothelial cell dysfunction and low platelet counts have been described. Thrombocytopenia is a common feature in VHF syndromes, and it is a major sign for its diagnosis. However, the underlying pathogenic mechanism has not yet been elucidated. We hypothesized that thrombocytopenia results from a viral-triggered alteration of the megakaryo/thrombopoiesis process. Therefore, we evaluated the impact of JUNV on megakaryopoiesis using an in vitro model of human CD34<sup>+</sup> cells stimulated with thrombopoietin. Our results showed that CD34<sup>+</sup> cells are infected with JUNV in a restricted fashion. Infection was transferrin receptor 1 (TfR1)-dependent and the surface expression of TfR1 was higher in infected cultures, suggesting a novel arenaviral dissemination strategy in hematopoietic progenitor cells. Although proliferation, survival, and commitment in JUNV-infected cultures were normal, viral infection impaired thrombopoiesis by decreasing in vitro proplatelet formation, platelet release, and P-selectin externalization via a bystander effect. The decrease in platelet release was also TfR1-dependent, mimicked by poly(I:C), and type I interferon (IFN α/ß) was implicated as a key paracrine mediator. Among the relevant molecules studied, only the transcription factor NF-E2 showed a moderate decrease in expression in megakaryocytes from either infected cultures or after type I IFN treatment. Moreover, type I IFN-treated megakaryocytes presented ultrastructural abnormalities resembling the reported thrombocytopenic NF-E2<sup>-/-</sup> mouse phenotype. Our study introduces a potential mechanism for thrombocytopenia in VHF and other diseases associated with increased bone marrow type I IFN levels.
format Articulo
Articulo
author Pozner, Roberto G.
Ure, Agustín Enrique
Jaquenod De Giusti, Carolina
D'Atri, Lina P.
Italiano, Joseph E.
Torres, Oscar
Romanowski, Víctor
Schattner, Mirta
Gómez, Ricardo Martín
author_facet Pozner, Roberto G.
Ure, Agustín Enrique
Jaquenod De Giusti, Carolina
D'Atri, Lina P.
Italiano, Joseph E.
Torres, Oscar
Romanowski, Víctor
Schattner, Mirta
Gómez, Ricardo Martín
author_sort Pozner, Roberto G.
title Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling
title_short Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling
title_full Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling
title_fullStr Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling
title_full_unstemmed Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling
title_sort junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type i ifn signaling
publishDate 2010
url http://sedici.unlp.edu.ar/handle/10915/29442
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000847
work_keys_str_mv AT poznerrobertog juninvirusinfectionofhumanhematopoieticprogenitorsimpairsinvitroproplateletformationandplateletreleaseviaabystandereffectinvolvingtypeiifnsignaling
AT ureagustinenrique juninvirusinfectionofhumanhematopoieticprogenitorsimpairsinvitroproplateletformationandplateletreleaseviaabystandereffectinvolvingtypeiifnsignaling
AT jaquenoddegiusticarolina juninvirusinfectionofhumanhematopoieticprogenitorsimpairsinvitroproplateletformationandplateletreleaseviaabystandereffectinvolvingtypeiifnsignaling
AT datrilinap juninvirusinfectionofhumanhematopoieticprogenitorsimpairsinvitroproplateletformationandplateletreleaseviaabystandereffectinvolvingtypeiifnsignaling
AT italianojosephe juninvirusinfectionofhumanhematopoieticprogenitorsimpairsinvitroproplateletformationandplateletreleaseviaabystandereffectinvolvingtypeiifnsignaling
AT torresoscar juninvirusinfectionofhumanhematopoieticprogenitorsimpairsinvitroproplateletformationandplateletreleaseviaabystandereffectinvolvingtypeiifnsignaling
AT romanowskivictor juninvirusinfectionofhumanhematopoieticprogenitorsimpairsinvitroproplateletformationandplateletreleaseviaabystandereffectinvolvingtypeiifnsignaling
AT schattnermirta juninvirusinfectionofhumanhematopoieticprogenitorsimpairsinvitroproplateletformationandplateletreleaseviaabystandereffectinvolvingtypeiifnsignaling
AT gomezricardomartin juninvirusinfectionofhumanhematopoieticprogenitorsimpairsinvitroproplateletformationandplateletreleaseviaabystandereffectinvolvingtypeiifnsignaling
bdutipo_str Repositorios
_version_ 1764820468156596226

Ejemplares similares