Cargando…

Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection

Congenital Zika Syndrome (CZS) is caused by vertical transmission of Zika virus (ZIKV) to the gestating human fetus. A subset of CZS microcephalic infants present with reduced otoacoustic emissions; this test screens for hearing loss originating in the cochlea. This observation leads to the question...

Descripción completa

Detalles Bibliográficos
Autores principales: Munnamalai, Vidhya, Sammudin, Nabilah H., Young, Caryl A., Thawani, Ankita, Kuhn, Richard J., Fekete, Donna M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472928/
https://www.ncbi.nlm.nih.gov/pubmed/34578404
http://dx.doi.org/10.3390/v13091823
_version_ 1784574860238782464
author Munnamalai, Vidhya
Sammudin, Nabilah H.
Young, Caryl A.
Thawani, Ankita
Kuhn, Richard J.
Fekete, Donna M.
author_facet Munnamalai, Vidhya
Sammudin, Nabilah H.
Young, Caryl A.
Thawani, Ankita
Kuhn, Richard J.
Fekete, Donna M.
author_sort Munnamalai, Vidhya
collection PubMed
description Congenital Zika Syndrome (CZS) is caused by vertical transmission of Zika virus (ZIKV) to the gestating human fetus. A subset of CZS microcephalic infants present with reduced otoacoustic emissions; this test screens for hearing loss originating in the cochlea. This observation leads to the question of whether mammalian cochlear tissues are susceptible to infection by ZIKV during development. To address this question using a mouse model, the sensory cochlea was explanted at proliferative, newly post-mitotic or maturing stages. ZIKV was added for the first 24 h and organs cultured for up to 6 days to allow for cell differentiation. Results showed that ZIKV can robustly infect proliferating sensory progenitors, as well as post-mitotic hair cells and supporting cells. Virus neutralization using ZIKV-117 antibody blocked cochlear infection. AXL is a cell surface molecule known to enhance the attachment of flavivirus to host cells. While Axl mRNA is widely expressed in embryonic cochlear tissues susceptible to ZIKV infection, it is selectively downregulated in the post-mitotic sensory organ by E15.5, even though these cells remain infectible. These findings may offer insights into which target cells could potentially contribute to hearing loss resulting from fetal exposure to ZIKV in humans.
format Online
Article
Text
id pubmed-8472928
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84729282021-09-28 Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection Munnamalai, Vidhya Sammudin, Nabilah H. Young, Caryl A. Thawani, Ankita Kuhn, Richard J. Fekete, Donna M. Viruses Article Congenital Zika Syndrome (CZS) is caused by vertical transmission of Zika virus (ZIKV) to the gestating human fetus. A subset of CZS microcephalic infants present with reduced otoacoustic emissions; this test screens for hearing loss originating in the cochlea. This observation leads to the question of whether mammalian cochlear tissues are susceptible to infection by ZIKV during development. To address this question using a mouse model, the sensory cochlea was explanted at proliferative, newly post-mitotic or maturing stages. ZIKV was added for the first 24 h and organs cultured for up to 6 days to allow for cell differentiation. Results showed that ZIKV can robustly infect proliferating sensory progenitors, as well as post-mitotic hair cells and supporting cells. Virus neutralization using ZIKV-117 antibody blocked cochlear infection. AXL is a cell surface molecule known to enhance the attachment of flavivirus to host cells. While Axl mRNA is widely expressed in embryonic cochlear tissues susceptible to ZIKV infection, it is selectively downregulated in the post-mitotic sensory organ by E15.5, even though these cells remain infectible. These findings may offer insights into which target cells could potentially contribute to hearing loss resulting from fetal exposure to ZIKV in humans. MDPI 2021-09-14 /pmc/articles/PMC8472928/ /pubmed/34578404 http://dx.doi.org/10.3390/v13091823 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Munnamalai, Vidhya
Sammudin, Nabilah H.
Young, Caryl A.
Thawani, Ankita
Kuhn, Richard J.
Fekete, Donna M.
Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection
title Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection
title_full Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection
title_fullStr Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection
title_full_unstemmed Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection
title_short Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection
title_sort embryonic and neonatal mouse cochleae are susceptible to zika virus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472928/
https://www.ncbi.nlm.nih.gov/pubmed/34578404
http://dx.doi.org/10.3390/v13091823
work_keys_str_mv AT munnamalaividhya embryonicandneonatalmousecochleaearesusceptibletozikavirusinfection
AT sammudinnabilahh embryonicandneonatalmousecochleaearesusceptibletozikavirusinfection
AT youngcaryla embryonicandneonatalmousecochleaearesusceptibletozikavirusinfection
AT thawaniankita embryonicandneonatalmousecochleaearesusceptibletozikavirusinfection
AT kuhnrichardj embryonicandneonatalmousecochleaearesusceptibletozikavirusinfection
AT feketedonnam embryonicandneonatalmousecochleaearesusceptibletozikavirusinfection