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Modelling SARS-CoV-2 Infection in Mice Using Lentiviral hACE2 Vectors Suggests Two Modes of Immune Responses to SARS-CoV-2 Infection

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of individuals worldwide, causing a severe global pandemic. Mice models are wildly used to investigate viral infection pathology, antiviral drugs, and vaccine development. However, since wild-type mice do not express human angiotensin-converting enzyme 2 (hACE2), which mediates SARS-CoV-2 entry into human cells, they are not susceptible to infection with SARS-CoV-2 and are not suitable to simulate symptomatic COVID-19 disease. HACE2 transgenic mice could provide an efficient model, but they are expensive, not always readily available and practically restricted to specific strain(s). Since additional models are needed to study the disease at varying genetic and immune backgrounds, there is a dearth of mouse models for SARS-CoV-2 infection. Here we report the application of lentiviral vectors to generate hACE2 expression in mouse lung epithelial cells (LET1) as well as in interferon receptor knock-out (IFNAR1-/-) mice. Lenti-hACE2 transduction supported SARS-CoV-2 replication both in vitro and in vivo, simulating mild acute lung disease1. Gene expression analysis revealed two modes of immune responses to SARS-CoV-2 infection: one in response to the exposure of mouse lungs to SARS-CoV-2 particles in the absence of productive viral replication, and the second in response to a productive infection. This approach expands our knowledge on the role of type-1 interferon signaling in COVID-19 disease, and can be further implemented for a range of COVID-19 studies and drug development.

ORGANISM(S): Mus musculus

PROVIDER: GSE186167 | GEO | 2021/12/07

REPOSITORIES: GEO

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