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Modeling SARS-CoV-2 Infection in Mice Using Lentiviral hACE2 Vectors Infers Two Modes of Immune Responses to SARS-CoV-2 Infection
| Content Provider | MDPI |
|---|---|
| Author | Katzman, Chaja Israely, Tomer Melamed, Sharon Politi, Boaz Sittner, Assa Yahalom-Ronen, Yfat Weiss, Shay Rass, Reem Abu Zamostiano, Rachel Bacharach, Eran Ehrlich, Marcelo Paran, Nir Nissim, Lior |
| Copyright Year | 2021 |
| Description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a severe global pandemic. Mice models are essential to investigate infection pathology, antiviral drugs, and vaccine development. However, wild-type mice lack the human angiotensin-converting enzyme 2 (hACE2) that mediates SARS-CoV-2 entry into human cells and consequently are not susceptible to SARS-CoV-2 infection. hACE2 transgenic mice could provide an efficient COVID-19 model, but are not always readily available, and practically restricted to specific strains. Therefore, there is a dearth of additional mouse models for SARS-CoV-2 infection. We applied lentiviral vectors to generate hACE2 expression in interferon receptor knock-out $(IFNAR1^{−/−}$) mice. Lenti-hACE2 transduction supported SARS-CoV-2 replication in vivo, simulating mild acute lung disease. 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 productive SARS-CoV-2 infection. Our results infer that immune response to immunogenic elements on incoming virus or in productively infected cells stimulate diverse immune effectors, even in absence of type I IFN signaling. Our findings should contribute to a better understanding of the immune response triggered by SARS-CoV-2 and to further elucidate COVID-19. |
| Starting Page | 11 |
| e-ISSN | 19994915 |
| DOI | 10.3390/v14010011 |
| Journal | Viruses |
| Issue Number | 1 |
| Volume Number | 14 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-12-21 |
| Access Restriction | Open |
| Subject Keyword | Viruses Immunology Sars-cov-2 Covid-19 Hace2 Lentivirus Mouse Model Immune Response |
| Content Type | Text |
| Resource Type | Article |
