{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:38:50Z","timestamp":1760236730468,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Milner Foundation","award":["3175005849"],"award-info":[{"award-number":["3175005849"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u2212\/\u2212) 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.<\/jats:p>","DOI":"10.3390\/v14010011","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T01:08:09Z","timestamp":1640135289000},"page":"11","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modeling SARS-CoV-2 Infection in Mice Using Lentiviral hACE2 Vectors Infers Two Modes of Immune Responses to SARS-CoV-2 Infection"],"prefix":"10.3390","volume":"14","author":[{"given":"Chaja","family":"Katzman","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomer","family":"Israely","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Melamed","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boaz","family":"Politi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1633-8191","authenticated-orcid":false,"given":"Assa","family":"Sittner","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yfat","family":"Yahalom-Ronen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shay","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9614-3847","authenticated-orcid":false,"given":"Reem","family":"Abu Rass","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Zamostiano","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8341-2833","authenticated-orcid":false,"given":"Eran","family":"Bacharach","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2352-1808","authenticated-orcid":false,"given":"Marcelo","family":"Ehrlich","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nir","family":"Paran","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6495-4741","authenticated-orcid":false,"given":"Lior","family":"Nissim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. Rev. 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