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nature portfolio privacy policy editing goat anti-rabbit-ap developed advertising sars-cov-2 infection-induced mortality15 sars-cov-2-infected mice suggest sars-cov-2-infected c57bl/6 wt post-infection media k18 hace2 transgenic mice angiotensin-converting enzyme 2 k18-hace2 mice infected reprints nature https interferon-gamma-related cytokine storm middle human ace2-transgenic mice enzyme-linked immunosorbent assays acute lps-induced inflammation26 recent research sars-cov-2 develop severe goat anti-rabbit-alexa 488 sars-cov-2 nucleocapsid protein c57bl/6 wt-infected mice wt-infected c57bl/6 mice facilitates amino-acid transport5 nature nature 581 research community research design survived sars-cov-2 infection sars-cov-2 infected hamsters sars-cov-2-infected wt full-length human ace2 mice specific-pathogen-free helper-dependent adenoviral vectors end-stage covid-19 outcomes central nervous system sars-cov-2 infection [asymptomatic sars-cov-2 infection leads establishing sars-cov-2 infection post-influenza bacterial superinfections thermofisher scientific social media k18 hace2 transgenic k18 transgenic hace2 male sars-cov-2-infected sars-cov-2-infected patients original author sars-cov-2 infection protects

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         headline:Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice
         description:Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease. Here, the authors characterize tissue-level SARS-CoV-2 infection and pathogenesis in transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18-hACE2) and show that infection induces lethality, making the K18-hACE2 model suitable for vaccine and therapeutic evaluation.
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      headline:Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice
      description:Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease. Here, the authors characterize tissue-level SARS-CoV-2 infection and pathogenesis in transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18-hACE2) and show that infection induces lethality, making the K18-hACE2 model suitable for vaccine and therapeutic evaluation.
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      url:http://orcid.org/0000-0001-7046-7683
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      name:Edward J. Dick
      url:http://orcid.org/0000-0003-2373-7921
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      name:Shannan Hall-Ursone
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      name:Larry S. Schlesinger
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      name:Xavier Alvarez
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      name:Deepak Kaushal
      url:http://orcid.org/0000-0003-3521-1257
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      name:Luis D. Giavedoni
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      name:Joanne Turner
      url:http://orcid.org/0000-0002-0840-7484
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Luis Martinez-Sobrido
      url:http://orcid.org/0000-0001-7084-0804
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Jordi B. Torrelles
      url:http://orcid.org/0000-0001-7702-5941
      affiliation:
            name:Texas Biomedical Research Institute
            address:
               name:Texas Biomedical Research Institute, San Antonio, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Integrated Biomedical Sciences Program, University of Texas Health Science Center at San Antonio, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Integrated Biomedical Sciences Program, University of Texas Health Science Center at San Antonio, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Integrated Biomedical Sciences Program, University of Texas Health Science Center at San Antonio, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA
      name:Texas Biomedical Research Institute, San Antonio, USA

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