Modeling sars-cov-2 infection in mice using lentiviral hace2 vectors infers two modes of immune responses to sars-cov-2 infection

Chaja Katzman, Tomer Israely, Sharon Melamed, Boaz Politi, Assa Sittner, Yfat Yahalom-Ronen, Shay Weiss, Reem Abu Rass, Rachel Zamostiano, Eran Bacharach, Marcelo Ehrlich, Nir Paran, Lior Nissim

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number11
JournalViruses
Volume14
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • COVID-19
  • HACE2
  • Immune response
  • Lentivirus
  • Mouse model
  • SARS-CoV-2

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