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Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication
With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538748/ https://www.ncbi.nlm.nih.gov/pubmed/37769001 http://dx.doi.org/10.1371/journal.pone.0291146 |
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author | Gordhan, Bhavna Gowan Herrera, Carolina Pillay, Azure-Dee Seiphetlo, Thabiso Ealand, Christopher Shawn Machowski, Edith Singh, Natasha Seatholo, Ntombexolo Otwombe, Kennedy Lebina, Limakatso Frise, Rebecca Scarlatti, Gabriella Chiodi, Francesca Martinson, Neil Fox, Julie Kana, Bavesh Davandra |
author_facet | Gordhan, Bhavna Gowan Herrera, Carolina Pillay, Azure-Dee Seiphetlo, Thabiso Ealand, Christopher Shawn Machowski, Edith Singh, Natasha Seatholo, Ntombexolo Otwombe, Kennedy Lebina, Limakatso Frise, Rebecca Scarlatti, Gabriella Chiodi, Francesca Martinson, Neil Fox, Julie Kana, Bavesh Davandra |
author_sort | Gordhan, Bhavna Gowan |
collection | PubMed |
description | With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication. Nasal or oral tissue samples were collected from eligible participants and explants generated from the tissue were infected with various SARS-CoV-2 strains, including IC19 (lineage B.1.13), Beta (lineage B.1.351) and Delta (lineage B.1.617.2). A qRT-PCR assay used to measure viral replication in the tissue explants over a 15-day period, demonstrated no replication for any viral strains tested. Based on this, the ex vivo challenge protocol was modified by reducing the viral infection time and duration of sampling. Despite these changes, viral infectivity of the nasal and oral mucosa was not improved. Since 67% of the enrolled participants were already vaccinated against SARS-CoV-2, it is possible that neutralizing antibodies in explant tissue may have prevented the establishment of infection. However, we were unable to optimize plaque assays aimed at titrating the virus in supernatants from both infected and uninfected tissue, due to limited volume of culture supernatant available at the various collection time points. Currently, the reasons for the inability of these mucosal tissue samples to support replication of SARS-CoV-2 ex vivo remains unclear and requires further investigation. |
format | Online Article Text |
id | pubmed-10538748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105387482023-09-29 Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication Gordhan, Bhavna Gowan Herrera, Carolina Pillay, Azure-Dee Seiphetlo, Thabiso Ealand, Christopher Shawn Machowski, Edith Singh, Natasha Seatholo, Ntombexolo Otwombe, Kennedy Lebina, Limakatso Frise, Rebecca Scarlatti, Gabriella Chiodi, Francesca Martinson, Neil Fox, Julie Kana, Bavesh Davandra PLoS One Research Article With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication. Nasal or oral tissue samples were collected from eligible participants and explants generated from the tissue were infected with various SARS-CoV-2 strains, including IC19 (lineage B.1.13), Beta (lineage B.1.351) and Delta (lineage B.1.617.2). A qRT-PCR assay used to measure viral replication in the tissue explants over a 15-day period, demonstrated no replication for any viral strains tested. Based on this, the ex vivo challenge protocol was modified by reducing the viral infection time and duration of sampling. Despite these changes, viral infectivity of the nasal and oral mucosa was not improved. Since 67% of the enrolled participants were already vaccinated against SARS-CoV-2, it is possible that neutralizing antibodies in explant tissue may have prevented the establishment of infection. However, we were unable to optimize plaque assays aimed at titrating the virus in supernatants from both infected and uninfected tissue, due to limited volume of culture supernatant available at the various collection time points. Currently, the reasons for the inability of these mucosal tissue samples to support replication of SARS-CoV-2 ex vivo remains unclear and requires further investigation. Public Library of Science 2023-09-28 /pmc/articles/PMC10538748/ /pubmed/37769001 http://dx.doi.org/10.1371/journal.pone.0291146 Text en © 2023 Gordhan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gordhan, Bhavna Gowan Herrera, Carolina Pillay, Azure-Dee Seiphetlo, Thabiso Ealand, Christopher Shawn Machowski, Edith Singh, Natasha Seatholo, Ntombexolo Otwombe, Kennedy Lebina, Limakatso Frise, Rebecca Scarlatti, Gabriella Chiodi, Francesca Martinson, Neil Fox, Julie Kana, Bavesh Davandra Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication |
title | Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication |
title_full | Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication |
title_fullStr | Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication |
title_full_unstemmed | Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication |
title_short | Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication |
title_sort | evaluation of a human mucosal tissue explant model for sars-cov-2 replication |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538748/ https://www.ncbi.nlm.nih.gov/pubmed/37769001 http://dx.doi.org/10.1371/journal.pone.0291146 |
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