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Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection
HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovir...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398702/ https://www.ncbi.nlm.nih.gov/pubmed/34451403 http://dx.doi.org/10.3390/pathogens10080940 |
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author | Chitlaru, Theodor Bar-Haim, Erez Bar-On, Liat Rotem, Shahar Cohen, Hila Elia, Uri Gur, David Aftalion, Moshe Alkalay, Ron Makdasi, Efi Evgy, Yentl Falach, Reut Israeli, Ma’ayan Bercovich-Kinori, Adi Achdout, Hagit Yahalom-Ronen, Yfat Rosenfeld, Ronit Cohen, Ofer |
author_facet | Chitlaru, Theodor Bar-Haim, Erez Bar-On, Liat Rotem, Shahar Cohen, Hila Elia, Uri Gur, David Aftalion, Moshe Alkalay, Ron Makdasi, Efi Evgy, Yentl Falach, Reut Israeli, Ma’ayan Bercovich-Kinori, Adi Achdout, Hagit Yahalom-Ronen, Yfat Rosenfeld, Ronit Cohen, Ofer |
author_sort | Chitlaru, Theodor |
collection | PubMed |
description | HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovirus-mediated infection protocol for human ACE2 expression in HLA transgenic mice. Transient pulmonary expression of the human ACE2 receptor in these mice results in their sensitisation to SARS-CoV-2 infection, consequently providing a valuable animal model for COVID-19. Infection results in a transient loss in body weight starting 3 days post-infection, reaching 20–30% loss of weight at day 7 and full recovery at days 11–13 post-infection. The evolution of the disease revealed high reproducibility and very low variability among individual mice. The method was implemented in two different strains of HLA immunized mice. Infected animals developed strong protective humoral and cellular immune responses specific to the viral spike-protein, strictly depending on the adenovirus-mediated human ACE2 expression. Convalescent animals were protected against a subsequent re-infection with SARS-CoV-2, demonstrating that the model may be applied for assessment of efficacy of anti-viral immune responses. |
format | Online Article Text |
id | pubmed-8398702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83987022021-08-29 Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection Chitlaru, Theodor Bar-Haim, Erez Bar-On, Liat Rotem, Shahar Cohen, Hila Elia, Uri Gur, David Aftalion, Moshe Alkalay, Ron Makdasi, Efi Evgy, Yentl Falach, Reut Israeli, Ma’ayan Bercovich-Kinori, Adi Achdout, Hagit Yahalom-Ronen, Yfat Rosenfeld, Ronit Cohen, Ofer Pathogens Communication HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovirus-mediated infection protocol for human ACE2 expression in HLA transgenic mice. Transient pulmonary expression of the human ACE2 receptor in these mice results in their sensitisation to SARS-CoV-2 infection, consequently providing a valuable animal model for COVID-19. Infection results in a transient loss in body weight starting 3 days post-infection, reaching 20–30% loss of weight at day 7 and full recovery at days 11–13 post-infection. The evolution of the disease revealed high reproducibility and very low variability among individual mice. The method was implemented in two different strains of HLA immunized mice. Infected animals developed strong protective humoral and cellular immune responses specific to the viral spike-protein, strictly depending on the adenovirus-mediated human ACE2 expression. Convalescent animals were protected against a subsequent re-infection with SARS-CoV-2, demonstrating that the model may be applied for assessment of efficacy of anti-viral immune responses. MDPI 2021-07-26 /pmc/articles/PMC8398702/ /pubmed/34451403 http://dx.doi.org/10.3390/pathogens10080940 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 | Communication Chitlaru, Theodor Bar-Haim, Erez Bar-On, Liat Rotem, Shahar Cohen, Hila Elia, Uri Gur, David Aftalion, Moshe Alkalay, Ron Makdasi, Efi Evgy, Yentl Falach, Reut Israeli, Ma’ayan Bercovich-Kinori, Adi Achdout, Hagit Yahalom-Ronen, Yfat Rosenfeld, Ronit Cohen, Ofer Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection |
title | Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection |
title_full | Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection |
title_fullStr | Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection |
title_full_unstemmed | Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection |
title_short | Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection |
title_sort | implementation of adenovirus-mediated pulmonary expression of human ace2 in hla transgenic mice enables establishment of a covid-19 murine model for assessment of immune responses to sars-cov-2 infection |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398702/ https://www.ncbi.nlm.nih.gov/pubmed/34451403 http://dx.doi.org/10.3390/pathogens10080940 |
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