Comparison of Transgenic and Adenovirus hACE2 Mouse Models for SARS-CoV-2 Infection.

BioRxiv : the Preprint Server for Biology
Raveen RathnasingheMelissa B Uccellini

Abstract

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2)(1-3). Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in both the lung and brain leading to lethality. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the lung, and no clinical signs of infection with a challenge dose of 10 4 plaque forming units. The K18-hACE2 model provides a stringent model for testing the ability of vaccines and antivirals ...Continue Reading

Citations

Sep 24, 2020·Nature·Florian Krammer
Sep 24, 2020·Nature·César Muñoz-FontelaDan H Barouch
Sep 18, 2020·Oncoimmunology·Cléa MelenotteLaurence Zitvogel
Dec 2, 2020·Nature Communications·Fatai S OladunniJordi B Torrelles
Feb 13, 2021·Life Science Alliance·Prabhuanand SelvarajTony T Wang
Oct 28, 2020·Nature Protocols·Channabasavaiah B GurumurthyMasato Ohtsuka
May 7, 2021·Scientific Reports·C Joaquín CáceresDaniel R Perez

Methods Mentioned

BETA
transgenic
flow cytometry

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