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dc.contributor.authorRathnasinghe, Raveen
dc.contributor.authorStrohmeier, Shirin
dc.contributor.authorAmanat, Fatima
dc.contributor.authorGillespie, Virginia L
dc.contributor.authorKrammer, Florian
dc.contributor.authorGarcía-Sastre, Adolfo
dc.contributor.authorCoughlan, Lynda
dc.contributor.authorSchotsaert, Michael
dc.contributor.authorUccellini, Melissa B
dc.date.accessioned2020-11-18T16:25:43Z
dc.date.available2020-11-18T16:25:43Z
dc.date.issued2020-11-06en_US
dc.identifier.urihttp://hdl.handle.net/10713/14105
dc.description.abstractSevere acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2) [1-3]. Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection. The K18-hACE2 model provides a stringent model for testing vaccines and antivirals, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.en_US
dc.description.urihttps://doi.org/10.1080/22221751.2020.1838955en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofEmerging Microbes & Infectionsen_US
dc.subjectACE2en_US
dc.subjectCOVID-19en_US
dc.subjectSARS-CoV-2en_US
dc.subjectadenovirusen_US
dc.subjectmouse modelsen_US
dc.titleComparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infectionen_US
dc.typeArticleen_US
dc.identifier.doi10.1080/22221751.2020.1838955
dc.identifier.pmid33073694
dc.source.volume9
dc.source.issue1
dc.source.beginpage2433
dc.source.endpage2445
dc.source.countryUnited States


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