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
Affiliations
Chaja Katzman
Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
Tomer Israely
Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel
Sharon Melamed
Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel
Boaz Politi
Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel
Assa Sittner
Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel
Yfat Yahalom-Ronen
Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel
Shay Weiss
Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel
Reem Abu Rass
Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel-Aviv 69978, Israel
Rachel Zamostiano
Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel-Aviv 69978, Israel
Eran Bacharach
Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel-Aviv 69978, Israel
Marcelo Ehrlich
Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel-Aviv 69978, Israel
Nir Paran
Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel
Lior Nissim
Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
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.