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dc.contributor.authorZaid, Ali
dc.date.accessioned2021-04-27T01:44:50Z
dc.date.available2021-04-27T01:44:50Z
dc.date.issued2019
dc.identifier.issn2150-7511
dc.identifier.doi10.1128/mBio.00819-21
dc.identifier.urihttp://hdl.handle.net/10072/403969
dc.description.abstractNewly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has caused extensive mortality and morbidity and wreaked havoc on socioeconomic structures. The urgent need to better understand SARS-CoV-2 biology and enable continued development of effective countermeasures is aided by the production of laboratory tools that facilitate SARS-CoV-2 research. We previously created a directly accessible SARS-CoV-2 toolkit containing user-friendly reverse genetic (RG) infectious clones of SARS-CoV-2. Here, using K18-human ACE2 (hACE2) mice, we confirmed the validity of RG-rescued SARS-CoV-2 viruses to reproduce the infection profile, clinical disease, and pathogenesis already established in mice infected with natural SARS-CoV-2 isolates, often patient derived. RG-rescued SARS-CoV-2-infected K18-hACE2 mice developed substantial clinical disease and weight loss by day 6 postinfection. RG-rescued SARS-CoV-2 was recovered from the lungs and brains of infected K18-hACE2 mice, and infection resulted in viral pneumonia with considerable changes in lung pathology, as seen previously with natural SARS-CoV-2 infection. In mice infected with RG-rescued SARS-CoV-2-mCherry, mCherry was detected in areas of lung consolidation and colocalized with clinically relevant SARS-CoV-2-assocated immunopathology. RG-rescued SARS-CoV-2 viruses successfully recapitulated many of the features of severe COVID-19 associated with the K18-hACE2 model of SARS-CoV-2 infection. With utility in vivo, the RG-rescued SARS-CoV-2 viruses will be valuable resources to advance numerous areas of SARS-CoV-2 basic research and COVID-19 vaccine development.IMPORTANCE To develop COVID-19 countermeasures, powerful research tools are essential. We produced a SARS-COV-2 reverse genetic (RG) infectious clone toolkit that will benefit a variety of investigations. In this study, we further prove the toolkit's value by demonstrating the in vivo utility of RG-rescued SARS-CoV-2 isolates. RG-rescued SARS-CoV-2 isolates reproduce disease signs and pathology characteristic of the K18-hACE2 mouse model of severe COVID-19 in infected mice. Having been validated as a model of severe COVID-19 previously using only natural SARS-CoV-2 isolated from patients, this is the first investigation of RG-rescued SARS-CoV-2 viruses in K18-hACE2 mice. The RG-rescued SARS-CoV-2 viruses will facilitate basic understanding of SARS-CoV-2 and the preclinical development of COVID-19 therapeutics.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherAmerican Society for Microbiology
dc.relation.ispartofpagefrome00819-21
dc.relation.ispartofissue2
dc.relation.ispartofjournalmBio
dc.relation.ispartofvolume12
dc.subject.fieldofresearchVirology
dc.subject.fieldofresearchInfectious Agents
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchcode060506
dc.subject.fieldofresearchcode060502
dc.subject.fieldofresearchcode0605
dc.subject.keywordscoronavirus
dc.subject.keywordscytokines
dc.subject.keywordsinfectious clones
dc.subject.keywordslung infection
dc.subject.keywordsrespiratory viruses
dc.titleInfectious clones produce SARS-CoV-2 that causes severe pulmonary disease in infected K18-hACE2 mice
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationZaid, A, Infectious clones produce SARS-CoV-2 that causes severe pulmonary disease in infected K18-hACE2 mice, mBio, 2019, 12 (2), pp. e00819-21
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2021-04-26T10:25:16Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2021 Liu et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorZaid, Ali
gro.griffith.authorTaylor, Adam
gro.griffith.authorMcMillan, Nigel
gro.griffith.authorMahalingam, Suresh
gro.griffith.authorLiu, Xiang
gro.griffith.authorFreitas, Joseph R.


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