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Article: A SCID mouse-human lung xenograft model of SARS-CoV-2 infection

TitleA SCID mouse-human lung xenograft model of SARS-CoV-2 infection
Authors
KeywordsSARS-CoV-2
infection
human lung
xenograft
humanized mouse model
Issue Date2021
PublisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/
Citation
Theranostics, 2021, v. 11 n. 13, p. 6607-6615 How to Cite?
AbstractSARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo. Methods: Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Results: Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. Conclusions: These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.
Persistent Identifierhttp://hdl.handle.net/10722/304167
ISSN
2023 Impact Factor: 12.4
2023 SCImago Journal Rankings: 2.912
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFu, W-
dc.contributor.authorWang, W-
dc.contributor.authorYuan, L-
dc.contributor.authorLin, Y-
dc.contributor.authorHuang, X-
dc.contributor.authorChen, R-
dc.contributor.authorCai, M-
dc.contributor.authorLiu, C-
dc.contributor.authorChen, L-
dc.contributor.authorZhou, M-
dc.contributor.authorWu, K-
dc.contributor.authorZhao, H-
dc.contributor.authorPan, D-
dc.contributor.authorMa, J-
dc.contributor.authorHong, J-
dc.contributor.authorZhai, B-
dc.contributor.authorZhang, Y-
dc.contributor.authorKong, Z-
dc.contributor.authorWang, Y-
dc.contributor.authorChen, Y-
dc.contributor.authorYuan, Q-
dc.contributor.authorZhu, H-
dc.contributor.authorCheng, T-
dc.contributor.authorGuan, Y-
dc.contributor.authorXia, N-
dc.date.accessioned2021-09-23T08:56:09Z-
dc.date.available2021-09-23T08:56:09Z-
dc.date.issued2021-
dc.identifier.citationTheranostics, 2021, v. 11 n. 13, p. 6607-6615-
dc.identifier.issn1838-7640-
dc.identifier.urihttp://hdl.handle.net/10722/304167-
dc.description.abstractSARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo. Methods: Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Results: Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. Conclusions: These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.-
dc.languageeng-
dc.publisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/-
dc.relation.ispartofTheranostics-
dc.rightsTheranostics. Copyright © Ivyspring International Publisher.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectSARS-CoV-2-
dc.subjectinfection-
dc.subjecthuman lung-
dc.subjectxenograft-
dc.subjecthumanized mouse model-
dc.titleA SCID mouse-human lung xenograft model of SARS-CoV-2 infection-
dc.typeArticle-
dc.identifier.emailZhu, H: zhuhch@hku.hk-
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hk-
dc.identifier.authorityZhu, H=rp01535-
dc.identifier.authorityGuan, Y=rp00397-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7150/thno.58321-
dc.identifier.pmid33995679-
dc.identifier.pmcidPMC8120224-
dc.identifier.scopuseid_2-s2.0-85106149214-
dc.identifier.hkuros325412-
dc.identifier.volume11-
dc.identifier.issue13-
dc.identifier.spage6607-
dc.identifier.epage6615-
dc.identifier.isiWOS:000663788300006-
dc.publisher.placeAustralia-

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