| First Author | Rawle DJ | Year | 2021 |
| Journal | PLoS Pathog | Volume | 17 |
| Issue | 7 | Pages | e1009723 |
| PubMed ID | 34214142 | Mgi Jnum | J:336007 |
| Mgi Id | MGI:6816145 | Doi | 10.1371/journal.ppat.1009723 |
| Citation | Rawle DJ, et al. (2021) ACE2-lentiviral transduction enables mouse SARS-CoV-2 infection and mapping of receptor interactions. PLoS Pathog 17(7):e1009723 |
| abstractText | 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. |
