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Mice Humanized for MHC and hACE2 with High Permissiveness to SARS-CoV-2 Omicron Replication
Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not interact efficiently with SARS-CoV-2 Spike and therefore the laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here,...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s). Published by Elsevier Masson SAS on behalf of Institut Pasteur.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113602/ https://www.ncbi.nlm.nih.gov/pubmed/37080384 http://dx.doi.org/10.1016/j.micinf.2023.105142 |
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author | Le Chevalier, Fabien Authié, Pierre Chardenoux, Sébastien Bourgine, Maryline Vesin, Benjamin Cussigh, Delphine Sassier, Yohann Fert, Ingrid Noirat, Amandine Nemirov, Kirill Anna, François Bérard, Marion Guinet, Françoise Hardy, David Charneau, Pierre Lemonnier, François Langa-Vives, Francina Majlessi, Laleh |
author_facet | Le Chevalier, Fabien Authié, Pierre Chardenoux, Sébastien Bourgine, Maryline Vesin, Benjamin Cussigh, Delphine Sassier, Yohann Fert, Ingrid Noirat, Amandine Nemirov, Kirill Anna, François Bérard, Marion Guinet, Françoise Hardy, David Charneau, Pierre Lemonnier, François Langa-Vives, Francina Majlessi, Laleh |
author_sort | Le Chevalier, Fabien |
collection | PubMed |
description | Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not interact efficiently with SARS-CoV-2 Spike and therefore the laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated new hACE2 transgenic mice, which harbor the hACE2 gene under the human keratin 18 promoter, in “HHD-DR1” background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human populations. We selected three transgenic strains, with various hACE2 mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. These new hACE2 transgenic strains display high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants, while the previously available B6.K18-ACE2(2Prlmn/JAX) mice have been reported to be poorly susceptible to infection with Omicron. As a first application, one of these MHC- and ACE2-humanized strains was successfully used to show the efficacy of a lentiviral-based COVID-19 vaccine. |
format | Online Article Text |
id | pubmed-10113602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Author(s). Published by Elsevier Masson SAS on behalf of Institut Pasteur. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101136022023-04-19 Mice Humanized for MHC and hACE2 with High Permissiveness to SARS-CoV-2 Omicron Replication Le Chevalier, Fabien Authié, Pierre Chardenoux, Sébastien Bourgine, Maryline Vesin, Benjamin Cussigh, Delphine Sassier, Yohann Fert, Ingrid Noirat, Amandine Nemirov, Kirill Anna, François Bérard, Marion Guinet, Françoise Hardy, David Charneau, Pierre Lemonnier, François Langa-Vives, Francina Majlessi, Laleh Microbes Infect Original Article Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not interact efficiently with SARS-CoV-2 Spike and therefore the laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated new hACE2 transgenic mice, which harbor the hACE2 gene under the human keratin 18 promoter, in “HHD-DR1” background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human populations. We selected three transgenic strains, with various hACE2 mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. These new hACE2 transgenic strains display high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants, while the previously available B6.K18-ACE2(2Prlmn/JAX) mice have been reported to be poorly susceptible to infection with Omicron. As a first application, one of these MHC- and ACE2-humanized strains was successfully used to show the efficacy of a lentiviral-based COVID-19 vaccine. The Author(s). Published by Elsevier Masson SAS on behalf of Institut Pasteur. 2023-04-19 /pmc/articles/PMC10113602/ /pubmed/37080384 http://dx.doi.org/10.1016/j.micinf.2023.105142 Text en © 2023 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Original Article Le Chevalier, Fabien Authié, Pierre Chardenoux, Sébastien Bourgine, Maryline Vesin, Benjamin Cussigh, Delphine Sassier, Yohann Fert, Ingrid Noirat, Amandine Nemirov, Kirill Anna, François Bérard, Marion Guinet, Françoise Hardy, David Charneau, Pierre Lemonnier, François Langa-Vives, Francina Majlessi, Laleh Mice Humanized for MHC and hACE2 with High Permissiveness to SARS-CoV-2 Omicron Replication |
title | Mice Humanized for MHC and hACE2 with High Permissiveness to SARS-CoV-2 Omicron Replication |
title_full | Mice Humanized for MHC and hACE2 with High Permissiveness to SARS-CoV-2 Omicron Replication |
title_fullStr | Mice Humanized for MHC and hACE2 with High Permissiveness to SARS-CoV-2 Omicron Replication |
title_full_unstemmed | Mice Humanized for MHC and hACE2 with High Permissiveness to SARS-CoV-2 Omicron Replication |
title_short | Mice Humanized for MHC and hACE2 with High Permissiveness to SARS-CoV-2 Omicron Replication |
title_sort | mice humanized for mhc and hace2 with high permissiveness to sars-cov-2 omicron replication |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113602/ https://www.ncbi.nlm.nih.gov/pubmed/37080384 http://dx.doi.org/10.1016/j.micinf.2023.105142 |
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