In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 2 ( 2023-2-22), p. e1011168-
Abstract:
Angiotensin-converting enzyme 2 (ACE2), part of the renin-angiotensin system (RAS), serves as an entry point for SARS-CoV-2, leading to viral proliferation in permissive cell types. Using mouse lines in which the Ace2 locus has been humanized by syntenic replacement, we show that regulation of basal and interferon induced ACE2 expression, relative expression levels of different ACE2 transcripts, and sexual dimorphism in ACE2 expression are unique to each species, differ between tissues, and are determined by both intragenic and upstream promoter elements. Our results indicate that the higher levels of expression of ACE2 observed in the lungs of mice relative to humans may reflect the fact that the mouse promoter drives expression of ACE2 in populous airway club cells while the human promoter drives expression in alveolar type 2 (AT2) cells. In contrast to transgenic mice in which human ACE2 is expressed in ciliated cells under the control of the human FOXJ1 promoter, mice expressing ACE2 in club cells under the control of the endogenous Ace2 promoter show a robust immune response after infection with SARS-CoV-2, leading to rapid clearance of the virus. This supports a model in which differential expression of ACE2 determines which cell types in the lung are infected, and this in turn modulates the host response and outcome of COVID-19.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011168
DOI:
10.1371/journal.ppat.1011168.g001
DOI:
10.1371/journal.ppat.1011168.g002
DOI:
10.1371/journal.ppat.1011168.g003
DOI:
10.1371/journal.ppat.1011168.g004
DOI:
10.1371/journal.ppat.1011168.g005
DOI:
10.1371/journal.ppat.1011168.g006
DOI:
10.1371/journal.ppat.1011168.g007
DOI:
10.1371/journal.ppat.1011168.g008
DOI:
10.1371/journal.ppat.1011168.g009
DOI:
10.1371/journal.ppat.1011168.s001
DOI:
10.1371/journal.ppat.1011168.s002
DOI:
10.1371/journal.ppat.1011168.s003
DOI:
10.1371/journal.ppat.1011168.s004
DOI:
10.1371/journal.ppat.1011168.s005
DOI:
10.1371/journal.ppat.1011168.s006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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