In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 7 ( 2021-7-2), p. e1009723-
Abstract:
SARS-CoV-2 uses the human ACE2 (hACE2) receptor for cell attachment and entry, with mouse ACE2 (mACE2) unable to support infection. Herein we describe an ACE2-lentivirus system and illustrate its utility for in vitro and in vivo SARS-CoV-2 infection models. Transduction of non-permissive cell lines with hACE2 imparted replication competence, and transduction with mACE2 containing N30D, N31K, F83Y and H353K substitutions, to match hACE2, rescued SARS-CoV-2 replication. Intrapulmonary hACE2-lentivirus transduction of C57BL/6J mice permitted significant virus replication in lung epithelium. RNA-Seq and histological analyses illustrated that this model involved an acute inflammatory disease followed by resolution and tissue repair, with a transcriptomic profile similar to that seen in COVID-19 patients. hACE2-lentivirus transduction of IFNAR -/- and IL-28RA -/- mouse lungs was used to illustrate that loss of type I or III interferon responses have no significant effect on virus replication. However, their importance in driving inflammatory responses was illustrated by RNA-Seq analyses. We also demonstrate the utility of the hACE2-lentivirus transduction system for vaccine evaluation in C57BL/6J mice. The ACE2-lentivirus system thus has broad application in SARS-CoV-2 research, providing a tool for both mutagenesis studies and mouse model development.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009723
DOI:
10.1371/journal.ppat.1009723.g001
DOI:
10.1371/journal.ppat.1009723.g002
DOI:
10.1371/journal.ppat.1009723.g003
DOI:
10.1371/journal.ppat.1009723.g004
DOI:
10.1371/journal.ppat.1009723.g005
DOI:
10.1371/journal.ppat.1009723.g006
DOI:
10.1371/journal.ppat.1009723.g007
DOI:
10.1371/journal.ppat.1009723.s001
DOI:
10.1371/journal.ppat.1009723.s002
DOI:
10.1371/journal.ppat.1009723.s003
DOI:
10.1371/journal.ppat.1009723.s004
DOI:
10.1371/journal.ppat.1009723.s005
DOI:
10.1371/journal.ppat.1009723.s006
DOI:
10.1371/journal.ppat.1009723.s007
DOI:
10.1371/journal.ppat.1009723.s008
DOI:
10.1371/journal.ppat.1009723.s009
DOI:
10.1371/journal.ppat.1009723.s010
DOI:
10.1371/journal.ppat.1009723.s011
DOI:
10.1371/journal.ppat.1009723.s012
DOI:
10.1371/journal.ppat.1009723.s013
DOI:
10.1371/journal.ppat.1009723.s014
DOI:
10.1371/journal.ppat.1009723.s015
DOI:
10.1371/journal.ppat.1009723.s016
DOI:
10.1371/journal.ppat.1009723.r001
DOI:
10.1371/journal.ppat.1009723.r002
DOI:
10.1371/journal.ppat.1009723.r003
DOI:
10.1371/journal.ppat.1009723.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
Permalink