Congenital Zika Syndrome and Extra-Central Nervous System Detection of Zika Virus in a Pre-term Newborn in Mexico.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
05 03 2019
Historique:
received: 19 01 2018
accepted: 30 07 2018
pubmed: 7 9 2018
medline: 2 5 2020
entrez: 7 9 2018
Statut: ppublish

Résumé

During pregnancy, the Zika virus (ZIKV) replicates in the placenta and central nervous system (CNS) of infected fetuses; nevertheless, the ability of ZIKV to replicate in other fetal tissues has not been extensively characterized. We researched whether dissemination of congenitally-acquired ZIKV outside the CNS exists by searching for the accumulation of the viral envelope protein, ZIKV ribonucleic acid (RNA), and infectious viral particles in different organs of a deceased newborn with Congenital Zika Syndrome. A real-time qualitative polymerase chain reaction (qPCR) was used to detect ZIKV RNA in the brain, thymus, lungs, kidneys, adrenal glands, spleen, liver, and small intestine. The same tissues were analyzed by indirect immunofluorescence and immunoperoxidase assays using the monoclonal antibody 4G2 to detect ZIKV envelope antigens. Isolation of infectious ZIKV in a cell culture was carried out using brain and kidney samples. A postmortem, virological analysis of multiple organs, such as the kidneys (epithelial cells in the renal tubules), lungs (bronchial epithelia), thymus (epithelial cells inside the Hassall's corpuscles), and brain (neurons, ependymal cells, and macrophages) revealed the presence of ZIKV RNA and envelope antigens. Other tissues of the deceased newborn tested positive by qPCR for Epstein-Barr virus and human herpesvirus 6, including the brain cortex (Epstein-Barr) and the thymus, kidneys, and adrenal glands (human herpesvirus 6). The kidneys were identified as a significant niche for viral replication, given that infectious particles were successfully isolated from renal tissues. Our findings demonstrate the ability of congenitally-acquired ZIKV to produce disseminated infections and the viral tropism towards epithelial cells.

Sections du résumé

BACKGROUND
During pregnancy, the Zika virus (ZIKV) replicates in the placenta and central nervous system (CNS) of infected fetuses; nevertheless, the ability of ZIKV to replicate in other fetal tissues has not been extensively characterized.
METHODS
We researched whether dissemination of congenitally-acquired ZIKV outside the CNS exists by searching for the accumulation of the viral envelope protein, ZIKV ribonucleic acid (RNA), and infectious viral particles in different organs of a deceased newborn with Congenital Zika Syndrome. A real-time qualitative polymerase chain reaction (qPCR) was used to detect ZIKV RNA in the brain, thymus, lungs, kidneys, adrenal glands, spleen, liver, and small intestine. The same tissues were analyzed by indirect immunofluorescence and immunoperoxidase assays using the monoclonal antibody 4G2 to detect ZIKV envelope antigens. Isolation of infectious ZIKV in a cell culture was carried out using brain and kidney samples.
RESULTS
A postmortem, virological analysis of multiple organs, such as the kidneys (epithelial cells in the renal tubules), lungs (bronchial epithelia), thymus (epithelial cells inside the Hassall's corpuscles), and brain (neurons, ependymal cells, and macrophages) revealed the presence of ZIKV RNA and envelope antigens. Other tissues of the deceased newborn tested positive by qPCR for Epstein-Barr virus and human herpesvirus 6, including the brain cortex (Epstein-Barr) and the thymus, kidneys, and adrenal glands (human herpesvirus 6). The kidneys were identified as a significant niche for viral replication, given that infectious particles were successfully isolated from renal tissues.
CONCLUSIONS
Our findings demonstrate the ability of congenitally-acquired ZIKV to produce disseminated infections and the viral tropism towards epithelial cells.

Identifiants

pubmed: 30188990
pii: 5090674
doi: 10.1093/cid/ciy616
pmc: PMC6399440
doi:

Substances chimiques

Antigens, Viral 0
RNA, Viral 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

903-912

Informations de copyright

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

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Auteurs

Maria Yolotzin Valdespino-Vázquez (MY)

Departamento de Anatomía Patológica, Instituto Nacional de Perinatología, Ciudad de Mexico, México.

Edgar E Sevilla-Reyes (EE)

Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de Mexico, México.

Rosalia Lira (R)

Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Unidad Médica de Alta Especialidad Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, México.

Martha Yocupicio-Monroy (M)

Universidad Autónoma de la Ciudad de México, Posgrado en Ciencias Genómicas, Ciudad de Mexico, México.

Elvira Piten-Isidro (E)

Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de Mexico, México.

Celia Boukadida (C)

Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de Mexico, México.

Rogelio Hernández-Pando (R)

Sección de Patología Experimental, Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico, México.

Juan David Soriano-Jimenez (JD)

Departamento de Anatomía Patológica, Instituto Nacional de Perinatología, Ciudad de Mexico, México.

Alma Herrera-Salazar (A)

Departamento de Infectología e Inmunología, Ciudad de Mexico, México.

Ricardo Figueroa-Damián (R)

Departamento de Infectología e Inmunología, Ciudad de Mexico, México.

Gustavo Reyes-Terán (G)

Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de Mexico, México.

Rodrigo Zamora-Escudero (R)

Dirección Médica, Ciudad de Mexico, México.

Jorge Arturo Cardona-Pérez (JA)

Dirección General, Instituto Nacional de Perinatología, Ciudad de Mexico, México.

Angélica Maldonado-Rodríguez (A)

Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Unidad Médica de Alta Especialidad Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de Mexico, México.

Elsa Romelia Moreno-Verduzco (ER)

Subdirección de Servicios Auxiliares de Diagnóstico, Instituto Nacional de Perinatología, Ciudad de Mexico, México.

Jesús Miguel Torres-Flores (JM)

Laboratorio de Virología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de Mexico, México.

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