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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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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 |
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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 |
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