Journal Article

ACE2-lentiviral transduction enables mouse SARS-CoV-2 infection and mapping of receptor interactions

Bishop, Cameron, Nguyen, Wilson, Modhiran, Naphak, Le, Thuy T., Dumenil, Troy, Tang, Bing, Rawle, Daniel J., Suhrbier, Andreas, Yan, Kexin, Watterson, Daniel, Hobson-Peters, Jody

2021

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ACE2 / Amino acids / Angiotensin-converting enzyme 2 / Animal models / Biology and life sciences / Cell adhesion / Cell culture / Cell lines / Cell receptors / Coronaviruses / COVID-19 / COVID-19 vaccines / Cystic fibrosis / Epithelium / Flow cytometry / Gene expression / Health aspects / Host-virus relationships / Infections / Inflammatory diseases / Interferon / Kinases / Lungs / Medical research / Medicine and health sciences / Mutagenesis / Pandemics / Receptors / Replication / Research and Analysis Methods / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Transcriptomics / Transduction / Vaccines / Viral diseases / Viruses