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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...

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