@article {3132779,
	title = {Modeling SARS-CoV-2 Infection in Mice Using Lentiviral hACE2 Vectors Infers Two Modes of Immune Responses to SARS-CoV-2 Infection},
	journal = {Viruses},
	volume = {14},
	number = {1},
	year = {2021},
	note = {Katzman, ChajaIsraely, TomerMelamed, SharonPoliti, BoazSittner, AssaYahalom-Ronen, YfatWeiss, ShayAbu Rass, ReemZamostiano, RachelBacharach, EranEhrlich, MarceloParan, NirNissim, Lioreng3175005849/The Milner FoundationResearch Support, Non-U.S. Gov{\textquoteright}tSwitzerlandViruses. 2021 Dec 21;14(1). pii: v14010011. doi: 10.3390/v14010011.},
	month = {Dec 21},
	edition = {2022/01/23},
	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.},
	keywords = {*covid-19, *Disease Models, Animal, *hACE2, *immune response, *lentivirus, *mouse model, *SARS-CoV-2, Angiotensin-Converting Enzyme 2/*genetics/metabolism, Animals, Cell Line, COVID-19/*immunology/virology, Humans, Immunity/genetics, Lentivirus/*genetics, Lung/immunology/virology, Mice, Mice, Transgenic, Receptor, Interferon alpha-beta/genetics, SARS-CoV-2/*physiology, Transduction, Genetic, Virus Replication},
	isbn = {1999-4915 (Electronic)1999-4915 (Linking)},
	url = {https://pubmed.ncbi.nlm.nih.gov/35062215/ },
	author = {Katzman, C. and Israely, T. and Melamed, S. and Politi, B. and Sittner, A. and Yahalom-Ronen, Y. and Weiss, S. and Abu Rass, R. and Zamostiano, R. and Bacharach, E. and Ehrlich, M. and Paran, N. and Nissim, L.}
}
