Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice.

Autor: Oladunni FS; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Park JG; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Pino PA; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Gonzalez O; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Akhter A; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Allué-Guardia A; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Olmo-Fontánez A; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA.; Integrated Biomedical Sciences Program, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA., Gautam S; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Garcia-Vilanova A; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Ye C; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Chiem K; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA.; Integrated Biomedical Sciences Program, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA., Headley C; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Dwivedi V; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Parodi LM; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Alfson KJ; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Staples HM; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Schami A; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA.; Integrated Biomedical Sciences Program, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA., Garcia JI; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Whigham A; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Platt RN 2nd; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Gazi M; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Martinez J; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Chuba C; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Earley S; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Rodriguez OH; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Mdaki SD; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Kavelish KN; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Escalona R; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Hallam CRA; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Christie C; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Patterson JL; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Anderson TJC; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Carrion R Jr; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Dick EJ Jr; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Hall-Ursone S; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Schlesinger LS; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Alvarez X; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Kaushal D; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Giavedoni LD; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA., Turner J; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA. joanneturner@txbiomed.org., Martinez-Sobrido L; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA. lmartinez@txbiomed.org., Torrelles JB; Texas Biomedical Research Institute, San Antonio, TX, 78227, USA. jtorrelles@txbiomed.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Nov 30; Vol. 11 (1), pp. 6122. Date of Electronic Publication: 2020 Nov 30.
DOI: 10.1038/s41467-020-19891-7
Abstrakt: 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.
Databáze: MEDLINE