Evidence map›Paper›PMID 34561300›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Analysis of SARS-CoV-2 infection dynamic in vivo using reporter-expressing viruses.

Chengjin Ye, Kevin Chiem, Jun-Gyu Park, Jesus A Silvas, Desarey Morales Vasquez, Julien Sourimant, Michelle J Lin, Alexander L Greninger, Richard K Plemper, Jordi B Torrelles and 4 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed.

  1. Article
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  4. Extra gene coding capacity of SARS-CoV-2 provides a virus engineering platform for in vitro and in vivo applications.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
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  7. Article
  8. Article
  9. Article
  10. A bireporter recombinant SARS-CoV-2 Omicron BA.5 forbioRxiv : the preprint server for biology · 2026
    Article
  11. Spatially structured models of viral dynamics: a scoping review.Microbiology and molecular biology reviews : MMBR · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Reporter-expressing viruses for antiviral drug discovery research.Frontiers in cellular and infection microbiology · 2025
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Chengjin YeHost-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX 78227; cye@txbiomed.org lmartinez@txbiomed.org.ORCID 0000-0002-1934-9494
Kevin ChiemHost-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX 78227.ORCID 0000-0002-3892-5944
Jun-Gyu ParkHost-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX 78227.ORCID 0000-0001-7163-3591
Jesus A SilvasHost-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX 78227.ORCID 0000-0002-1200-803X
Desarey Morales VasquezHost-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX 78227.ORCID 0000-0002-7357-9821
Julien SourimantCenter for Translational Antiviral Research, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303.
Michelle J LinVirology Division, Department of Laboratory Medicine, University of Washington, Seattle, WA 98195.
Alexander L GreningerVirology Division, Department of Laboratory Medicine, University of Washington, Seattle, WA 98195.
Richard K PlemperCenter for Translational Antiviral Research, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303.
Jordi B TorrellesHost-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX 78227.ORCID 0000-0001-7702-5941
James J KobieDepartment of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL 35294.ORCID 0000-0001-8069-0272
Mark R WalterDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294.ORCID 0000-0003-2163-5550
Juan Carlos de la TorreDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.ORCID 0000-0002-8171-8115
Luis Martinez-SobridoHost-Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX 78227; cye@txbiomed.org lmartinez@txbiomed.org.ORCID 0000-0001-7084-0804

Funding

Development of a Broad-Spectrum Inhibitor against Seasonal and Highly-Pathogenic Influenza VirusesR01AI141222 · NIAID · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2019 to 2023
$5.0M
The origin and future protective activity of SARS-CoV-2 RBD specific neutralizing antibodiesR01AI161175 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KOBIE, JAMES J, MARTINEZ-SOBRIDO, LUIS · 2021 to 2024
$2.5M
NIAID NIH HHS R01 AI141222NIAID NIH HHS R01 AI161175
6 · The paper itself

Abstract

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.

Indexed as

COVID-19Gene Expression Regulation, ViralGenes, ReporterSARS-CoV-2Viral ProteinsAngiotensin-Converting Enzyme 2AnimalsChlorocebus aethiopsCoronavirus Nucleocapsid ProteinsFemaleHumansMiceMice, TransgenicTeschovirusVero CellsACE2 protein, humanAngiotensin-Converting Enzyme 2Coronavirus Nucleocapsid ProteinsORF7a protein, SARS-CoV-2Viral ProteinsCOVID-19in vivo imagingreporter virusesSARS-CoV-2

Identifiers

PMID34561300
PMCPMC8521683

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.