Zika virus impairs the development of blood vessels in a mouse model of congenital infection

Autores
Garcez, P. P.; Stolp, H. B.; Sravanam, S.; Christoff, R. R.; Ferreira, J. C. C. G.; Dias, A. A.; Pezzuto, P.; Higa, L. M.; Barbeito Andrés, Jimena; Ferreira, R. O.; Andrade, C. B V.; Siqueira, M.; Santos, T. M. P.; Drumond, J.; Hoerder Suabedissen, A.; de Lima, C. V. F.; Tovar Moll, F.; Lopes, R. T.; Fragel Madeira, L.; Lent, R.; Ortiga Carvalho, T. M.; Stipursky, J.; Bellio, M.; Tanuri, A.; Molnár, Z.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.
Fil: Garcez, P. P.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Stolp, H. B.. University of Oxford; Reino Unido
Fil: Sravanam, S.. University of Oxford; Reino Unido
Fil: Christoff, R. R.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Ferreira, J. C. C. G.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Dias, A. A.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Pezzuto, P.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Higa, L. M.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Barbeito Andrés, Jimena. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina
Fil: Ferreira, R. O.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Andrade, C. B V.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Siqueira, M.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Santos, T. M. P.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Drumond, J.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Hoerder Suabedissen, A.. University of Oxford; Reino Unido
Fil: de Lima, C. V. F.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Tovar Moll, F.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Lopes, R. T.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Fragel Madeira, L.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Lent, R.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Ortiga Carvalho, T. M.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Stipursky, J.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Bellio, M.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Tanuri, A.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Molnár, Z.. University of Oxford; Reino Unido
Materia
STORCH
CEREBRAL CORTEX
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:11336/125497
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Zika virus impairs the development of blood vessels in a mouse model of congenital infectionGarcez, P. P.Stolp, H. B.Sravanam, S.Christoff, R. R.Ferreira, J. C. C. G.Dias, A. A.Pezzuto, P.Higa, L. M.Barbeito Andrés, JimenaFerreira, R. O.Andrade, C. B V.Siqueira, M.Santos, T. M. P.Drumond, J.Hoerder Suabedissen, A.de Lima, C. V. F.Tovar Moll, F.Lopes, R. T.Fragel Madeira, L.Lent, R.Ortiga Carvalho, T. M.Stipursky, J.Bellio, M.Tanuri, A.Molnár, Z.STORCHCEREBRAL CORTEXhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.Fil: Garcez, P. P.. Universidade Federal do Rio de Janeiro; BrasilFil: Stolp, H. B.. University of Oxford; Reino UnidoFil: Sravanam, S.. University of Oxford; Reino UnidoFil: Christoff, R. R.. Universidade Federal do Rio de Janeiro; BrasilFil: Ferreira, J. C. C. G.. Universidade Federal do Rio de Janeiro; BrasilFil: Dias, A. A.. Universidade Federal do Rio de Janeiro; BrasilFil: Pezzuto, P.. Universidade Federal do Rio de Janeiro; BrasilFil: Higa, L. M.. Universidade Federal do Rio de Janeiro; BrasilFil: Barbeito Andrés, Jimena. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Ferreira, R. O.. Universidade Federal do Rio de Janeiro; BrasilFil: Andrade, C. B V.. Universidade Federal do Rio de Janeiro; BrasilFil: Siqueira, M.. Universidade Federal do Rio de Janeiro; BrasilFil: Santos, T. M. P.. Universidade Federal do Rio de Janeiro; BrasilFil: Drumond, J.. Universidade Federal do Rio de Janeiro; BrasilFil: Hoerder Suabedissen, A.. University of Oxford; Reino UnidoFil: de Lima, C. V. F.. Universidade Federal do Rio de Janeiro; BrasilFil: Tovar Moll, F.. Universidade Federal do Rio de Janeiro; BrasilFil: Lopes, R. T.. Universidade Federal do Rio de Janeiro; BrasilFil: Fragel Madeira, L.. Universidade Federal do Rio de Janeiro; BrasilFil: Lent, R.. Universidade Federal do Rio de Janeiro; BrasilFil: Ortiga Carvalho, T. M.. Universidade Federal do Rio de Janeiro; BrasilFil: Stipursky, J.. Universidade Federal do Rio de Janeiro; BrasilFil: Bellio, M.. Universidade Federal do Rio de Janeiro; BrasilFil: Tanuri, A.. Universidade Federal do Rio de Janeiro; BrasilFil: Molnár, Z.. University of Oxford; Reino UnidoNature Publishing Group2018-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/125497Garcez, P. P.; Stolp, H. B.; Sravanam, S.; Christoff, R. R.; Ferreira, J. C. C. G.; et al.; Zika virus impairs the development of blood vessels in a mouse model of congenital infection; Nature Publishing Group; Scientifics Reports; 8; 12774; 8-2018; 1-102045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-018-31149-3info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-31149-3info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:49Zoai:ri.conicet.gov.ar:11336/125497instacron: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:34982025-09-03 10:00:49.626CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Zika virus impairs the development of blood vessels in a mouse model of congenital infection
title Zika virus impairs the development of blood vessels in a mouse model of congenital infection
spellingShingle Zika virus impairs the development of blood vessels in a mouse model of congenital infection
Garcez, P. P.
STORCH
CEREBRAL CORTEX
title_short Zika virus impairs the development of blood vessels in a mouse model of congenital infection
title_full Zika virus impairs the development of blood vessels in a mouse model of congenital infection
title_fullStr Zika virus impairs the development of blood vessels in a mouse model of congenital infection
title_full_unstemmed Zika virus impairs the development of blood vessels in a mouse model of congenital infection
title_sort Zika virus impairs the development of blood vessels in a mouse model of congenital infection
dc.creator.none.fl_str_mv Garcez, P. P.
Stolp, H. B.
Sravanam, S.
Christoff, R. R.
Ferreira, J. C. C. G.
Dias, A. A.
Pezzuto, P.
Higa, L. M.
Barbeito Andrés, Jimena
Ferreira, R. O.
Andrade, C. B V.
Siqueira, M.
Santos, T. M. P.
Drumond, J.
Hoerder Suabedissen, A.
de Lima, C. V. F.
Tovar Moll, F.
Lopes, R. T.
Fragel Madeira, L.
Lent, R.
Ortiga Carvalho, T. M.
Stipursky, J.
Bellio, M.
Tanuri, A.
Molnár, Z.
author Garcez, P. P.
author_facet Garcez, P. P.
Stolp, H. B.
Sravanam, S.
Christoff, R. R.
Ferreira, J. C. C. G.
Dias, A. A.
Pezzuto, P.
Higa, L. M.
Barbeito Andrés, Jimena
Ferreira, R. O.
Andrade, C. B V.
Siqueira, M.
Santos, T. M. P.
Drumond, J.
Hoerder Suabedissen, A.
de Lima, C. V. F.
Tovar Moll, F.
Lopes, R. T.
Fragel Madeira, L.
Lent, R.
Ortiga Carvalho, T. M.
Stipursky, J.
Bellio, M.
Tanuri, A.
Molnár, Z.
author_role author
author2 Stolp, H. B.
Sravanam, S.
Christoff, R. R.
Ferreira, J. C. C. G.
Dias, A. A.
Pezzuto, P.
Higa, L. M.
Barbeito Andrés, Jimena
Ferreira, R. O.
Andrade, C. B V.
Siqueira, M.
Santos, T. M. P.
Drumond, J.
Hoerder Suabedissen, A.
de Lima, C. V. F.
Tovar Moll, F.
Lopes, R. T.
Fragel Madeira, L.
Lent, R.
Ortiga Carvalho, T. M.
Stipursky, J.
Bellio, M.
Tanuri, A.
Molnár, Z.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv STORCH
CEREBRAL CORTEX
topic STORCH
CEREBRAL CORTEX
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.
Fil: Garcez, P. P.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Stolp, H. B.. University of Oxford; Reino Unido
Fil: Sravanam, S.. University of Oxford; Reino Unido
Fil: Christoff, R. R.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Ferreira, J. C. C. G.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Dias, A. A.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Pezzuto, P.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Higa, L. M.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Barbeito Andrés, Jimena. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina
Fil: Ferreira, R. O.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Andrade, C. B V.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Siqueira, M.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Santos, T. M. P.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Drumond, J.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Hoerder Suabedissen, A.. University of Oxford; Reino Unido
Fil: de Lima, C. V. F.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Tovar Moll, F.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Lopes, R. T.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Fragel Madeira, L.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Lent, R.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Ortiga Carvalho, T. M.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Stipursky, J.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Bellio, M.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Tanuri, A.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Molnár, Z.. University of Oxford; Reino Unido
description Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.
publishDate 2018
dc.date.none.fl_str_mv 2018-08
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/11336/125497
Garcez, P. P.; Stolp, H. B.; Sravanam, S.; Christoff, R. R.; Ferreira, J. C. C. G.; et al.; Zika virus impairs the development of blood vessels in a mouse model of congenital infection; Nature Publishing Group; Scientifics Reports; 8; 12774; 8-2018; 1-10
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/125497
identifier_str_mv Garcez, P. P.; Stolp, H. B.; Sravanam, S.; Christoff, R. R.; Ferreira, J. C. C. G.; et al.; Zika virus impairs the development of blood vessels in a mouse model of congenital infection; Nature Publishing Group; Scientifics Reports; 8; 12774; 8-2018; 1-10
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-018-31149-3
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-31149-3
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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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score 13.13397

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