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

Maria Yolotzin Valdespino-Vázquez, Edgar E. Sevilla-Reyes, Rosalia Lira, Martha Yocupicio-Monroy, Elvira Piten-Isidro, Celia Boukadida, Rogelio Hernández-Pando, Juan David Soriano-Jimenez, Alma Herrera-Salazar, Ricardo Figueroa-Damián, Gustavo Reyes-Terán, Rodrigo Zamora-Escudero, Jorge Arturo Cardona-Pérez, Angélica Maldonado-Rodríguez, Elsa Romelia Moreno-Verduzco, Jesús Miguel Torres-Flores

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)903-912
Number of pages10
JournalClinical Infectious Diseases
Volume68
Issue number6
DOIs
StatePublished - 5 Mar 2019

Keywords

  • Zika virus
  • co-infection
  • congenital Zika syndrome
  • dissemination

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