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DOI	10.1073/pnas.2111593118
	Analysis of SARS-CoV-2 infection dynamic in vivo using reporter-expressing viruses
	Ye C.; Chiem K.; Park J.-G.; Silvas J.A.; Vasquez D.M.; Sourimant J.; Lin M.J.; Greninger A.L.; Plemper R.K.; Torrelles J.B.; Kobie J.J.; Walter M.R.; de la Torre J.C.; Martinez-Sobrido L.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:41
英文摘要	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, is one of the biggest threats to public health. However, the dynamic of SARS-CoV-2 infection remains poorly understood. Replication-competent recombinant viruses expressing reporter genes provide valuable tools to investigate viral infection. Low levels of reporter gene expressed from previous reporter-expressing recombinant (r)SARS-CoV-2 in the locus of the open reading frame (ORF)7a protein have jeopardized their use to monitor the dynamic of SARS-CoV-2 infection in vitro or in vivo. Here, we report an alternative strategy where reporter genes were placed upstream of the highly expressed viral nucleocapsid (N) gene followed by a porcine tescherovirus (PTV-1) 2A proteolytic cleavage site. The higher levels of reporter expression using this strategy resulted in efficient visualization of rSARS-CoV-2 in infected cultured cells and excised lungs or whole organism of infected K18 human angiotensin converting enzyme 2 (hACE2) transgenic mice. Importantly, real-time viral infection was readily tracked using a noninvasive in vivo imaging system and allowed us to rapidly identify antibodies which are able to neutralize SARS-CoV-2 infection in vivo. Notably, these reporter-expressing rSARS-CoV-2, in which a viral gene was not deleted, not only retained wild-type (WT) virus-like pathogenicity in vivo but also exhibited high stability in vitro and in vivo, supporting their use to investigate viral infection, dissemination, pathogenesis, and therapeutic interventions for the treatment of SARS-CoV-2 in vivo. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	COVID-19; In vivo imaging; Reporter viruses; SARS-CoV-2
语种	英语
scopus关键词	ACE2 protein, human; ORF7a protein, SARS-CoV-2; viral protein; animal; biosynthesis; Chlorocebus aethiops; female; gene expression regulation; genetics; human; metabolism; mouse; reporter gene; Teschovirus; transgenic mouse; Vero cell line; Angiotensin-Converting Enzyme 2; Animals; Chlorocebus aethiops; Coronavirus Nucleocapsid Proteins; COVID-19; Female; Gene Expression Regulation, Viral; Genes, Reporter; Humans; Mice; Mice, Transgenic; SARS-CoV-2; Teschovirus; Vero Cells; Viral Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251006
作者单位	Host-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX 78227, United States; Population Health Program, Texas Biomedical Research Institute, San Antonio, TX 78227, United States; Center for Translational Antiviral Research, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, United States; Virology Division, Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, United States; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Immunology and Microbiology, The Scripps Research Institute, San Diego, CA 92037, United States
推荐引用方式 GB/T 7714	Ye C.,Chiem K.,Park J.-G.,et al. Analysis of SARS-CoV-2 infection dynamic in vivo using reporter-expressing viruses[J],2021,118(41).
APA	Ye C..,Chiem K..,Park J.-G..,Silvas J.A..,Vasquez D.M..,...&Martinez-Sobrido L..(2021).Analysis of SARS-CoV-2 infection dynamic in vivo using reporter-expressing viruses.Proceedings of the National Academy of Sciences of the United States of America,118(41).
MLA	Ye C.,et al."Analysis of SARS-CoV-2 infection dynamic in vivo using reporter-expressing viruses".Proceedings of the National Academy of Sciences of the United States of America 118.41(2021).