K18-hACE2 mice develop respiratory disease resembling severe COVID-19

SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-1...

Full description

Saved in:
Bibliographic Details
Published inPLoS pathogens Vol. 17; no. 1; p. e1009195
Main Authors Yinda, Claude Kwe, Port, Julia R., Bushmaker, Trenton, Offei Owusu, Irene, Purushotham, Jyothi N., Avanzato, Victoria A., Fischer, Robert J., Schulz, Jonathan E., Holbrook, Myndi G., Hebner, Madison J., Rosenke, Rebecca, Thomas, Tina, Marzi, Andrea, Best, Sonja M., de Wit, Emmie, Shaia, Carl, van Doremalen, Neeltje, Munster, Vincent J.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 19.01.2021
Public Library of Science (PLoS)
Subjects
Alveoli
Angiotensin-Converting Enzyme 2 - genetics
Angiotensin-Converting Enzyme 2 - immunology
Animals
Antigens
Biology and life sciences
Coronaviruses
COVID-19
COVID-19 - genetics
COVID-19 - immunology
COVID-19 - pathology
COVID-19 - virology
Cytokeratin
Disease Models, Animal
Dose-response relationship (Biochemistry)
Edema
Engineering and Technology
Epithelial cells
Female
Fibrin
Gastrointestinal system
Gastrointestinal tract
Gene expression
Genomes
Health aspects
Humans
Hyperplasia
Immunoreactivity
Infections
Inflammation
Irradiated
Keratin-18 - genetics
Keratin-18 - immunology
Kidneys
Leukocytes (neutrophilic)
Lung - immunology
Lung - pathology
Lungs
Lymphocytes
Lymphocytes - immunology
Macrophages
Macrophages - immunology
Male
Medicine and health sciences
Mice
Mice, Transgenic
Necrosis
Neutrophils
Organs
Pathology
Pneumocytes
Pneumonia
Promoter Regions, Genetic
Promoters (Genetics)
Rectum
Research and Analysis Methods
Respiratory diseases
SARS-CoV-2 - physiology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Shedding
Trachea - immunology
Trachea - virology
Transgenic animals
Viral diseases
Viruses
United States
Online AccessGet full text
ISSN1553-7374
1553-7366
1553-7374
DOI10.1371/journal.ppat.1009195

Cover

Abstract SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 10 4 TCID 50 or 10 5 TCID 50 , the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 10 5 TCID 50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 10 2 TCID 50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.
AbstractList SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 104 TCID50 or 105 TCID50, the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 105 TCID50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 102 TCID50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.
Expression of hACE2 is driven by a cytokeratin promoter in the airway epithelial cells as well as in epithelia of other internal organs, including the liver, kidney, gastrointestinal tract and brain. Blue: 104 TCID50 (low dose animals, n = 6); red: 105 TCID50 (high dose animals, n = 6); green: 105 TCID50 γ-irradiated (control animals, n = 2); dotted line = limit of detection. https://doi.org/10.1371/journal.ppat.1009195.g001 Viral shedding in SARS-CoV-2-inoculated K18-hACE mice To gain an understanding of dose-dependent virus shedding patterns of SARS-CoV-2 in infected K18-hACE2 mice, daily nasal, oropharyngeal and rectal swabs were obtained until 11 DPI. At 7 DPI, mice exhibit multifocal, and often peripheral, pulmonary pathology consistent with interstitial pneumonia characterized by type II pneumocyte hyperplasia, septal, alveolar and perivascular inflammation comprised of lymphocytes, macrophages and neutrophils, variable amounts of alveolar fibrin and edema, frequent syncytial cells and single cell necrosis (Fig 3I–3K). Pathological changes in lungs of K18-hACE mice inoculated with SARS-CoV-2 at 3 and 7 DPI. a, b, c, d. γ-irradiated SARS-CoV-2 inoculated control lungs appear normal and lack SARS-CoV-2 antigen immunoreactivity. e, f, g. Inflammation at 3 DPI, characterized by perivascular and septal infiltration by neutrophils, macrophages, lymphocytes, and edema. i, j, k. Multifocal interstitial pneumonia at 7 DPI, characterized by type II pneumocyte hyperplasia (arrowheads), alveolar and perivascular inflammation, fibrin, edema, syncytial cells (inset arrowheads) and single cell necrosis. h, l. SARS-CoV-2 antigen immunoreactivity in type I (arrowheads) and type II pneumocytes (arrows) at 3 and 7 DPI.
SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 10.sup.4 TCID.sub.50 or 10.sup.5 TCID.sub.50, the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 10.sup.5 TCID.sub.50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 10.sup.2 TCID.sub.50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.
SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 10 4 TCID 50 or 10 5 TCID 50 , the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 10 5 TCID 50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 10 2 TCID 50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development. The disease manifestation of COVID-19 in humans ranges from asymptomatic to severe. While several mild to moderate disease models have been developed, there is still a need for animal models that recapitulate the severe and fatal progression observed in a subset of patients. Here, we show that humanized transgenic mice developed dose-dependent disease when inoculated with SARS-CoV-2, the etiological agent of COVID-19. The mice developed upper and lower respiratory tract infection, with virus replication also in the brain after day 3 post inoculation. The pathological and immunological diseases manifestation observed in these mice bears resemblance to human COVID-19. This suggests increased usefulness of this model for elucidating COVID-19 pathogenesis and for testing of countermeasures, both of which are urgently needed.
Expression of hACE2 is driven by a cytokeratin promoter in the airway epithelial cells as well as in epithelia of other internal organs, including the liver, kidney, gastrointestinal tract and brain. Blue: 104 TCID50 (low dose animals, n = 6); red: 105 TCID50 (high dose animals, n = 6); green: 105 TCID50 γ-irradiated (control animals, n = 2); dotted line = limit of detection. https://doi.org/10.1371/journal.ppat.1009195.g001 Viral shedding in SARS-CoV-2-inoculated K18-hACE mice To gain an understanding of dose-dependent virus shedding patterns of SARS-CoV-2 in infected K18-hACE2 mice, daily nasal, oropharyngeal and rectal swabs were obtained until 11 DPI. At 7 DPI, mice exhibit multifocal, and often peripheral, pulmonary pathology consistent with interstitial pneumonia characterized by type II pneumocyte hyperplasia, septal, alveolar and perivascular inflammation comprised of lymphocytes, macrophages and neutrophils, variable amounts of alveolar fibrin and edema, frequent syncytial cells and single cell necrosis (Fig 3I–3K). Pathological changes in lungs of K18-hACE mice inoculated with SARS-CoV-2 at 3 and 7 DPI. a, b, c, d. γ-irradiated SARS-CoV-2 inoculated control lungs appear normal and lack SARS-CoV-2 antigen immunoreactivity. e, f, g. Inflammation at 3 DPI, characterized by perivascular and septal infiltration by neutrophils, macrophages, lymphocytes, and edema. i, j, k. Multifocal interstitial pneumonia at 7 DPI, characterized by type II pneumocyte hyperplasia (arrowheads), alveolar and perivascular inflammation, fibrin, edema, syncytial cells (inset arrowheads) and single cell necrosis. h, l. SARS-CoV-2 antigen immunoreactivity in type I (arrowheads) and type II pneumocytes (arrows) at 3 and 7 DPI.
SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 10 4 TCID 50 or 10 5 TCID 50 , the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 10 5 TCID 50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 10 2 TCID 50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.
SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 104 TCID50 or 105 TCID50, the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 105 TCID50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 102 TCID50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 104 TCID50 or 105 TCID50, the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 105 TCID50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 102 TCID50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.
Audience Academic
Author Port, Julia R.
Schulz, Jonathan E.
Holbrook, Myndi G.
Hebner, Madison J.
van Doremalen, Neeltje
Offei Owusu, Irene
Shaia, Carl
Thomas, Tina
Avanzato, Victoria A.
Yinda, Claude Kwe
Munster, Vincent J.
Rosenke, Rebecca
Fischer, Robert J.
Bushmaker, Trenton
Best, Sonja M.
Purushotham, Jyothi N.
Marzi, Andrea
de Wit, Emmie
AuthorAffiliation 1 Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America
2 Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America
The Peter Doherty Institute and Melbourne University, AUSTRALIA
AuthorAffiliation_xml – name: The Peter Doherty Institute and Melbourne University, AUSTRALIA
– name: 1 Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America
– name: 2 Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America
Author_xml – sequence: 1
  givenname: Claude Kwe
  orcidid: 0000-0002-5195-5478
  surname: Yinda
  fullname: Yinda, Claude Kwe
– sequence: 2
  givenname: Julia R.
  orcidid: 0000-0002-0489-6591
  surname: Port
  fullname: Port, Julia R.
– sequence: 3
  givenname: Trenton
  surname: Bushmaker
  fullname: Bushmaker, Trenton
– sequence: 4
  givenname: Irene
  orcidid: 0000-0002-8523-955X
  surname: Offei Owusu
  fullname: Offei Owusu, Irene
– sequence: 5
  givenname: Jyothi N.
  orcidid: 0000-0002-6190-4199
  surname: Purushotham
  fullname: Purushotham, Jyothi N.
– sequence: 6
  givenname: Victoria A.
  surname: Avanzato
  fullname: Avanzato, Victoria A.
– sequence: 7
  givenname: Robert J.
  orcidid: 0000-0002-1816-472X
  surname: Fischer
  fullname: Fischer, Robert J.
– sequence: 8
  givenname: Jonathan E.
  orcidid: 0000-0001-5462-5952
  surname: Schulz
  fullname: Schulz, Jonathan E.
– sequence: 9
  givenname: Myndi G.
  orcidid: 0000-0001-6669-0583
  surname: Holbrook
  fullname: Holbrook, Myndi G.
– sequence: 10
  givenname: Madison J.
  orcidid: 0000-0002-4415-762X
  surname: Hebner
  fullname: Hebner, Madison J.
– sequence: 11
  givenname: Rebecca
  orcidid: 0000-0003-3779-7423
  surname: Rosenke
  fullname: Rosenke, Rebecca
– sequence: 12
  givenname: Tina
  surname: Thomas
  fullname: Thomas, Tina
– sequence: 13
  givenname: Andrea
  orcidid: 0000-0003-0186-9587
  surname: Marzi
  fullname: Marzi, Andrea
– sequence: 14
  givenname: Sonja M.
  orcidid: 0000-0003-0206-297X
  surname: Best
  fullname: Best, Sonja M.
– sequence: 15
  givenname: Emmie
  orcidid: 0000-0002-9763-7758
  surname: de Wit
  fullname: de Wit, Emmie
– sequence: 16
  givenname: Carl
  orcidid: 0000-0001-8907-8821
  surname: Shaia
  fullname: Shaia, Carl
– sequence: 17
  givenname: Neeltje
  orcidid: 0000-0003-4368-6359
  surname: van Doremalen
  fullname: van Doremalen, Neeltje
– sequence: 18
  givenname: Vincent J.
  orcidid: 0000-0002-2288-3196
  surname: Munster
  fullname: Munster, Vincent J.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33465158$$D View this record in MEDLINE/PubMed
BookMark eNqVkktv1DAUhSNURB_wDxBEYgOLDL6xHTtdII2GAUZUVOK1tRznZuoqEwc7U9F_j8OkVaeqkFAWiW6-c2wfn-PkoHMdJslzIDOgAt5euq3vdDvrez3MgJASSv4oOQLOaSaoYAd3vg-T4xAuCWFAoXiSHFLKCg5cHiXLzyCzi_limacbazCt8Qpb16ceQ2-9Hpy_TmsbUAccZ7ipWtut0xAxj-ni_OfqfQbl0-Rxo9uAz6b3SfLjw_L74lN2dv5xtZifZUbkYshqBAO6EDLnjAtNc8mlBsS6qkpgVcPqQnJeS2qqsgbKcsFBVpJxWWlKyoqeJC93vn3rgpoSCCpnJaHAc15EYrUjaqcvVe_tRvtr5bRVfwfOr5X2gzUtKlFKjbmAqiA1Y4JrwjhqA3nJWW0ajF7vptW21QZrg93gdbtnuv-nsxdq7a6UkIJTJqPB68nAu19bDIPa2GCwbXWHbjvuW5QMSlJARF_dQx8-3UStdTyA7RoX1zWjqZoXnEiIUeWRmj1AxafGeMexRY2N8z3Bmz1BZAb8Paz1NgS1-vb1P9gv--yLuwHeJndTvwiwHWC8C8Fjc4sAUWPLb1JQY8vV1PIoO70nM3bQg3XjNdj23-I_RRgAEg
CitedBy_id crossref_primary_10_1038_s41467_021_21239_8
crossref_primary_10_1371_journal_ppat_1010741
crossref_primary_10_1016_j_tips_2022_02_010
crossref_primary_10_1177_03009858211071016
crossref_primary_10_1371_journal_ppat_1009758
crossref_primary_10_1128_spectrum_02371_22
crossref_primary_10_1016_j_micpath_2021_104836
crossref_primary_10_5319_wjo_v10_i2_4
crossref_primary_10_3390_v14081627
crossref_primary_10_1111_jpi_12772
crossref_primary_10_1038_s41541_023_00645_7
crossref_primary_10_3390_ijms25158245
crossref_primary_10_1016_j_bbih_2024_100905
crossref_primary_10_1007_s12015_022_10409_w
crossref_primary_10_1016_j_isci_2021_103670
crossref_primary_10_14348_molcells_2022_0089
crossref_primary_10_1038_s41564_021_01047_y
crossref_primary_10_3390_v14050966
crossref_primary_10_3390_vaccines10020251
crossref_primary_10_1016_j_virusres_2021_198563
crossref_primary_10_7554_eLife_98344_3
crossref_primary_10_1016_j_vaccine_2023_09_033
crossref_primary_10_1172_jci_insight_155896
crossref_primary_10_3390_microorganisms9040868
crossref_primary_10_3390_v14051020
crossref_primary_10_3390_cells12162107
crossref_primary_10_1080_22221751_2023_2178242
crossref_primary_10_3390_biomedicines10020351
crossref_primary_10_1016_j_immuni_2021_08_016
crossref_primary_10_3390_v16071158
crossref_primary_10_1099_jgv_0_002039
crossref_primary_10_1016_j_bbadis_2024_167347
crossref_primary_10_1016_j_isci_2022_105507
crossref_primary_10_1016_j_ajpath_2023_03_008
crossref_primary_10_1016_j_scitotenv_2022_160163
crossref_primary_10_1038_s42003_023_05626_z
crossref_primary_10_1097_CCE_0000000000001225
crossref_primary_10_1038_s41392_024_02007_8
crossref_primary_10_1186_s12985_023_02230_9
crossref_primary_10_2139_ssrn_4181455
crossref_primary_10_1093_cid_ciab903
crossref_primary_10_3389_fimmu_2022_950666
crossref_primary_10_1002_mds_29116
crossref_primary_10_1371_journal_ppat_1009064
crossref_primary_10_3390_biomedicines12091941
crossref_primary_10_3390_pathogens12010020
crossref_primary_10_1161_ATVBAHA_121_316925
crossref_primary_10_1371_journal_ppat_1012100
crossref_primary_10_1016_j_jhin_2021_12_010
crossref_primary_10_4110_in_2024_24_e7
crossref_primary_10_1021_acsomega_2c02794
crossref_primary_10_1016_j_antiviral_2021_105138
crossref_primary_10_1084_jem_20211862
crossref_primary_10_1080_22221751_2024_2353302
crossref_primary_10_1038_s44298_023_00012_2
crossref_primary_10_1186_s13567_024_01325_7
crossref_primary_10_1016_j_isci_2022_105038
crossref_primary_10_3389_fphar_2024_1351655
crossref_primary_10_1016_j_matpr_2021_11_013
crossref_primary_10_1038_s41467_021_25156_8
crossref_primary_10_1038_s42003_023_04689_2
crossref_primary_10_1073_pnas_2026785118
crossref_primary_10_1111_acel_13771
crossref_primary_10_26508_lsa_202301997
crossref_primary_10_3389_fimmu_2022_1055811
crossref_primary_10_3389_fmicb_2023_1320856
crossref_primary_10_1016_j_chom_2024_10_016
crossref_primary_10_1128_mbio_00683_22
crossref_primary_10_1371_journal_ppat_1011409
crossref_primary_10_1523_ENEURO_0106_24_2024
crossref_primary_10_1016_j_celrep_2022_110387
crossref_primary_10_1038_s41598_023_39628_y
crossref_primary_10_1371_journal_pone_0302344
crossref_primary_10_3389_fcimb_2022_841447
crossref_primary_10_1016_j_bbadis_2024_167322
crossref_primary_10_1016_j_medj_2022_08_002
crossref_primary_10_1126_science_abq0839
crossref_primary_10_1186_s13578_022_00770_1
crossref_primary_10_1371_journal_ppat_1010432
crossref_primary_10_1021_acsinfecdis_2c00091
crossref_primary_10_1016_j_isci_2023_105972
crossref_primary_10_1128_msphere_00243_22
crossref_primary_10_1371_journal_ppat_1009723
crossref_primary_10_3390_v15112151
crossref_primary_10_3390_cells11162572
crossref_primary_10_1371_journal_ppat_1011240
crossref_primary_10_3390_vaccines9111346
crossref_primary_10_1128_spectrum_04194_22
crossref_primary_10_3389_fphar_2024_1414406
crossref_primary_10_1134_S1990747825700035
crossref_primary_10_1172_jci_insight_152529
crossref_primary_10_3389_fimmu_2022_871276
crossref_primary_10_1016_j_ebiom_2021_103291
crossref_primary_10_7554_eLife_87094
crossref_primary_10_3389_fimmu_2022_1011185
crossref_primary_10_1186_s13054_022_04034_9
crossref_primary_10_1007_s00401_021_02314_2
crossref_primary_10_1016_j_celrep_2021_109452
crossref_primary_10_1038_s44298_024_00037_1
crossref_primary_10_1152_ajplung_00223_2021
crossref_primary_10_1038_s41467_021_23779_5
crossref_primary_10_1002_eji_202250332
crossref_primary_10_3389_fimmu_2022_948431
crossref_primary_10_1038_s41392_024_01917_x
crossref_primary_10_1038_s41598_022_21223_2
crossref_primary_10_1038_s43856_024_00610_y
crossref_primary_10_1128_aac_00341_24
crossref_primary_10_1128_jvi_02184_21
crossref_primary_10_1007_s00204_021_03214_w
crossref_primary_10_1016_j_bbr_2023_114662
crossref_primary_10_3389_fimmu_2022_820131
crossref_primary_10_3390_cells10071756
crossref_primary_10_1172_JCI159876
crossref_primary_10_1128_jvi_01194_23
crossref_primary_10_1016_j_celrep_2023_113275
crossref_primary_10_3390_nu13072216
crossref_primary_10_1038_s41467_022_34571_4
crossref_primary_10_1016_j_vaccine_2024_04_079
crossref_primary_10_1038_s41392_022_01087_8
crossref_primary_10_1128_spectrum_02687_22
crossref_primary_10_1371_journal_ppat_1009544
crossref_primary_10_1136_thoraxjnl_2021_217650
crossref_primary_10_3390_medicina59091554
crossref_primary_10_2139_ssrn_4172117
crossref_primary_10_1371_journal_ppat_1010092
crossref_primary_10_7554_eLife_87094_3
crossref_primary_10_1038_s41467_023_42346_8
crossref_primary_10_1134_S160767292201001X
crossref_primary_10_1016_j_virol_2024_109997
crossref_primary_10_3390_biomedicines11061736
crossref_primary_10_1016_j_isci_2022_104614
crossref_primary_10_1038_s41589_022_01094_4
crossref_primary_10_1038_s41467_022_33395_6
crossref_primary_10_3390_vaccines12080921
crossref_primary_10_3390_vaccines10040613
crossref_primary_10_1016_j_coviro_2023_101375
crossref_primary_10_1038_s41586_021_04342_0
crossref_primary_10_1126_scitranslmed_abo5070
crossref_primary_10_1038_s41541_023_00636_8
crossref_primary_10_1371_journal_ppat_1011614
crossref_primary_10_1016_j_bone_2021_116227
crossref_primary_10_1002_biot_202300130
crossref_primary_10_3389_fcimb_2021_679878
crossref_primary_10_1016_j_heliyon_2023_e19226
crossref_primary_10_1007_s00335_024_10033_8
crossref_primary_10_1038_s42003_024_06529_3
crossref_primary_10_1038_s41551_023_01054_w
crossref_primary_10_1128_Spectrum_00536_21
crossref_primary_10_3389_fimmu_2023_1223260
crossref_primary_10_1002_jmv_27747
crossref_primary_10_3390_v15010139
crossref_primary_10_1089_jamp_2022_0043
crossref_primary_10_1016_j_ebiom_2021_103704
crossref_primary_10_7554_eLife_98344
crossref_primary_10_1038_s41440_021_00800_4
crossref_primary_10_1128_JVI_01537_21
crossref_primary_10_1182_bloodadvances_2022007444
crossref_primary_10_3389_fmicb_2024_1348405
crossref_primary_10_1080_21505594_2024_2316438
crossref_primary_10_3390_v16121856
crossref_primary_10_1016_j_bbrc_2024_151224
crossref_primary_10_3390_antib10040045
crossref_primary_10_1371_journal_pone_0273430
crossref_primary_10_3389_fmicb_2024_1404312
crossref_primary_10_1038_s41598_023_29909_x
crossref_primary_10_1177_03009858221092015
crossref_primary_10_1073_pnas_2406332121
crossref_primary_10_1371_journal_pone_0294176
crossref_primary_10_1007_s11248_024_00413_w
crossref_primary_10_3390_vaccines12070766
crossref_primary_10_1038_s41541_022_00451_7
crossref_primary_10_3390_vaccines9080881
crossref_primary_10_1038_s41594_023_01023_6
crossref_primary_10_1128_msphere_00558_22
crossref_primary_10_3390_vaccines9111266
crossref_primary_10_3389_fbioe_2021_737627
crossref_primary_10_1038_s41467_023_40076_5
crossref_primary_10_1080_08830185_2022_2089666
crossref_primary_10_1016_j_isci_2021_102479
crossref_primary_10_1016_j_jtcms_2021_10_001
crossref_primary_10_3389_fcimb_2023_1307553
crossref_primary_10_3390_v15010123
crossref_primary_10_1007_s11914_022_00734_x
crossref_primary_10_1126_scitranslmed_abn6868
crossref_primary_10_1371_journal_ppat_1010867
crossref_primary_10_1371_journal_ppat_1012804
crossref_primary_10_1038_s41592_022_01427_0
crossref_primary_10_1016_j_intimp_2022_109325
crossref_primary_10_1038_s41541_022_00440_w
crossref_primary_10_1007_s11357_024_01102_6
crossref_primary_10_1007_s00011_024_01948_8
Cites_doi 10.4049/jimmunol.1202448
10.2807/1560-7917.ES.2020.25.3.2000045
10.1097/01.CCM.0000149854.61192.DC
10.1172/JCI137244
10.1016/j.phrs.2020.104833
10.1002/ame2.12108
10.1038/s41586-020-2012-7
10.1093/nsr/nwaa037
10.1016/S0140-6736(20)30183-5
10.1126/sciimmunol.abd6832
10.1016/j.jinf.2020.03.037
10.1016/j.ejrad.2020.109147
10.1371/journal.pone.0124080
10.1016/j.jtho.2020.02.010
10.1016/j.rmed.2020.105951
10.4269/ajtmh.18-0937
10.1016/j.chom.2020.03.023
10.1155/2017/6104054
10.1038/s41564-020-0688-y
10.1001/jama.2020.8907
10.1007/s11606-020-05762-w
10.1016/j.jaci.2020.04.027
10.1016/j.ajem.2007.10.031
10.1016/j.antiviral.2017.03.025
10.1128/JVI.02012-06
10.1038/s41591-020-0897-1
10.1126/science.abb7314
ContentType Journal Article
Copyright COPYRIGHT 2021 Public Library of Science
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: COPYRIGHT 2021 Public Library of Science
– notice: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
ISN
ISR
3V.
7QL
7U9
7X7
7XB
88E
8FE
8FH
8FI
8FJ
8FK
ABUWG
AEUYN
AFKRA
AZQEC
BBNVY
BENPR
BHPHI
C1K
CCPQU
COVID
DWQXO
FYUFA
GHDGH
GNUQQ
H94
HCIFZ
K9.
LK8
M0S
M1P
M7P
PHGZM
PHGZT
PIMPY
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
7X8
5PM
DOA
DOI 10.1371/journal.ppat.1009195
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Gale In Context: Canada
Gale In Context: Science
ProQuest Central (Corporate)
Bacteriology Abstracts (Microbiology B)
Virology and AIDS Abstracts
Health & Medical Collection (Proquest)
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
ProQuest SciTech Collection
ProQuest Natural Science Collection
ProQuest Hospital Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest One Sustainability
ProQuest Central UK/Ireland
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Natural Science Collection
Environmental Sciences and Pollution Management
ProQuest One Community College
Coronavirus Research Database
ProQuest Central
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
AIDS and Cancer Research Abstracts
SciTech Premium Collection
ProQuest Health & Medical Complete (Alumni)
ProQuest Biological Science Collection
Health & Medical Collection (Alumni Edition)
Medical Database
Biological Science Database
ProQuest Central Premium
ProQuest One Academic
Publicly Available Content (ProQuest)
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Publicly Available Content Database
ProQuest Central Student
ProQuest One Academic Middle East (New)
ProQuest Central Essentials
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Natural Science Collection
ProQuest Central China
Environmental Sciences and Pollution Management
ProQuest Central
ProQuest One Applied & Life Sciences
ProQuest One Sustainability
ProQuest Health & Medical Research Collection
Health Research Premium Collection
Health and Medicine Complete (Alumni Edition)
Natural Science Collection
ProQuest Central Korea
Bacteriology Abstracts (Microbiology B)
Health & Medical Research Collection
Biological Science Collection
AIDS and Cancer Research Abstracts
ProQuest Central (New)
ProQuest Medical Library (Alumni)
Virology and AIDS Abstracts
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
Coronavirus Research Database
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
Biological Science Database
ProQuest SciTech Collection
ProQuest Hospital Collection (Alumni)
ProQuest Health & Medical Complete
ProQuest Medical Library
ProQuest One Academic UKI Edition
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList
Publicly Available Content Database
MEDLINE



CrossRef
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 4
  dbid: BENPR
  name: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
DocumentTitleAlternate Severe respiratory disease in K18-hACE2 mice
EISSN 1553-7374
ExternalDocumentID 2490315256
oai_doaj_org_article_798ae271b60d4475a045eac12954dcfe
PMC7875348
A650814582
33465158
10_1371_journal_ppat_1009195
Genre Journal Article
Research Support, N.I.H., Intramural
GeographicLocations United States
GeographicLocations_xml – name: United States
GrantInformation_xml – fundername: Intramural NIH HHS
  grantid: 1ZIAAI00117901
– fundername: Intramural NIH HHS
  grantid: ZIA AI001179
– fundername: NIGMS NIH HHS
  grantid: T32 GM008169
– fundername: ;
  grantid: 1ZIAAI001179-01
GroupedDBID ---
123
29O
2WC
53G
5VS
7X7
88E
8FE
8FH
8FI
8FJ
AAFWJ
AAUCC
AAWOE
AAYXX
ABDBF
ABUWG
ACGFO
ACIHN
ACPRK
ACUHS
ADBBV
AEAQA
AENEX
AEUYN
AFKRA
AFPKN
AFRAH
AHMBA
ALMA_UNASSIGNED_HOLDINGS
AOIJS
B0M
BAWUL
BBNVY
BCNDV
BENPR
BHPHI
BPHCQ
BVXVI
BWKFM
CCPQU
CITATION
CS3
DIK
DU5
E3Z
EAP
EAS
EBD
EMK
EMOBN
ESX
F5P
FPL
FYUFA
GROUPED_DOAJ
GX1
HCIFZ
HMCUK
HYE
IAO
IHR
INH
INR
ISN
ISR
ITC
KQ8
LK8
M1P
M48
M7P
MM.
O5R
O5S
OK1
OVT
P2P
PGMZT
PHGZM
PHGZT
PIMPY
PQQKQ
PROAC
PSQYO
PV9
QF4
QN7
RNS
RPM
RZL
SV3
TR2
TUS
UKHRP
WOW
~8M
ADRAZ
CGR
CUY
CVF
ECM
EIF
H13
IPNFZ
NPM
PJZUB
PPXIY
PQGLB
RIG
WOQ
PMFND
3V.
7QL
7U9
7XB
8FK
AZQEC
C1K
COVID
DWQXO
GNUQQ
H94
K9.
PKEHL
PQEST
PQUKI
PRINS
7X8
5PM
PUEGO
-
AAPBV
ABPTK
ADACO
BBAFP
M~E
ID FETCH-LOGICAL-c727t-de1c1a67825457a32858a1eedbb914bf4d6855d83cb9d13427518b8458ba309b3
IEDL.DBID M48
ISSN 1553-7374
1553-7366
IngestDate Fri Nov 26 17:12:50 EST 2021
Wed Aug 27 01:26:44 EDT 2025
Thu Aug 21 18:41:53 EDT 2025
Fri Jul 11 09:32:45 EDT 2025
Fri Jul 25 10:39:40 EDT 2025
Tue Jun 17 21:00:34 EDT 2025
Tue Jun 10 20:46:38 EDT 2025
Fri Jun 27 04:03:42 EDT 2025
Fri Jun 27 04:11:19 EDT 2025
Mon Jul 21 05:35:25 EDT 2025
Tue Jul 01 04:24:28 EDT 2025
Thu Apr 24 22:56:48 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 1
Language English
License This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Creative Commons CC0 public domain
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c727t-de1c1a67825457a32858a1eedbb914bf4d6855d83cb9d13427518b8458ba309b3
Notes new_version
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
These authors share first authorship on this work.
The authors have declared that no competing interests exist.
ORCID 0000-0002-2288-3196
0000-0002-8523-955X
0000-0001-5462-5952
0000-0002-0489-6591
0000-0001-8907-8821
0000-0002-4415-762X
0000-0003-0186-9587
0000-0002-5195-5478
0000-0003-4368-6359
0000-0003-3779-7423
0000-0003-0206-297X
0000-0002-1816-472X
0000-0001-6669-0583
0000-0002-9763-7758
0000-0002-6190-4199
OpenAccessLink https://doaj.org/article/798ae271b60d4475a045eac12954dcfe
PMID 33465158
PQID 2490315256
PQPubID 1436335
ParticipantIDs plos_journals_2490315256
doaj_primary_oai_doaj_org_article_798ae271b60d4475a045eac12954dcfe
pubmedcentral_primary_oai_pubmedcentral_nih_gov_7875348
proquest_miscellaneous_2479419061
proquest_journals_2490315256
gale_infotracmisc_A650814582
gale_infotracacademiconefile_A650814582
gale_incontextgauss_ISR_A650814582
gale_incontextgauss_ISN_A650814582
pubmed_primary_33465158
crossref_primary_10_1371_journal_ppat_1009195
crossref_citationtrail_10_1371_journal_ppat_1009195
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2021-01-19
PublicationDateYYYYMMDD 2021-01-19
PublicationDate_xml – month: 01
  year: 2021
  text: 2021-01-19
  day: 19
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: San Francisco
– name: San Francisco, CA USA
PublicationTitle PLoS pathogens
PublicationTitleAlternate PLoS Pathog
PublicationYear 2021
Publisher Public Library of Science
Public Library of Science (PLoS)
Publisher_xml – name: Public Library of Science
– name: Public Library of Science (PLoS)
References Y Li (ppat.1009195.ref046) 2020; 157
B Schumak (ppat.1009195.ref049) 2015; 10
KH Dinnon (ppat.1009195.ref022) 2020
M Letko (ppat.1009195.ref015) 2020; 5
Jing Sun (ppat.1009195.ref018) 2020
Q Ye (ppat.1009195.ref025) 2020; 80
R Kolde (ppat.1009195.ref053) 2019
JF Chan (ppat.1009195.ref009) 2020
KD Cook (ppat.1009195.ref048) 2013; 190
L Chen (ppat.1009195.ref041) 2020; 43
Y Liu (ppat.1009195.ref039); 7
PB McCray (ppat.1009195.ref019) 2007; 81
F Jiang (ppat.1009195.ref005) 2020; 35
N Calcagno (ppat.1009195.ref006); 41
RD Jiang (ppat.1009195.ref032) 2020
JW Golden (ppat.1009195.ref034); 2020
F Feldmann (ppat.1009195.ref047) 2019; 100
QX Long (ppat.1009195.ref045) 2020; 26
Y Wu (ppat.1009195.ref029) 2020; 5
H Wang (ppat.1009195.ref042) 2008; 26
SH Sun (ppat.1009195.ref020) 2020
C Huang (ppat.1009195.ref026) 2020; 395
Y Yang (ppat.1009195.ref027); 146
PE Parsons (ppat.1009195.ref043) 2005; 33
BP Dhakal (ppat.1009195.ref007) 2020
VM Corman (ppat.1009195.ref050) 2020; 25
VJ Munster (ppat.1009195.ref011) 2020
P Zhou (ppat.1009195.ref016) 2020; 579
L Bao (ppat.1009195.ref030) 2020
B Rockx (ppat.1009195.ref014) 2020; 368
T Schaller (ppat.1009195.ref037) 2020; 323
GB Moreau (ppat.1009195.ref035); 2020
S Nie (ppat.1009195.ref002) 2020; 167
ppat.1009195.ref001
SE Fox (ppat.1009195.ref038); 2020
C Woolsey (ppat.1009195.ref012) 2020
S Wan (ppat.1009195.ref040); 2020
ppat.1009195.ref052
YI Kim (ppat.1009195.ref010) 2020; 27
Hongjing Gu (ppat.1009195.ref021) 2020
ASS Girija (ppat.1009195.ref044) 2020; 11
S Tian (ppat.1009195.ref036); 15
B Israelow (ppat.1009195.ref033) 2020
P Yu (ppat.1009195.ref013) 2020; 3
X Zhao (ppat.1009195.ref017) 2020
X Li (ppat.1009195.ref004); 24
ppat.1009195.ref054
AO Hassan (ppat.1009195.ref031) 2020
N van Doremalen (ppat.1009195.ref051) 2017; 143
JM Rojas (ppat.1009195.ref023) 2017; 2017
AH Parry (ppat.1009195.ref003) 2020; 129
L Mao (ppat.1009195.ref008) 2020
G Chen (ppat.1009195.ref024) 2020; 130
C Maucourant (ppat.1009195.ref028) 2020; 5
32803199 - bioRxiv. 2020 Aug 11:2020.08.11.246314. doi: 10.1101/2020.08.11.246314.
References_xml – year: 2020
  ident: ppat.1009195.ref030
  article-title: The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice
  publication-title: Nature
– volume: 190
  start-page: 641
  issue: 2
  year: 2013
  ident: ppat.1009195.ref048
  article-title: The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection
  publication-title: J Immunol
  doi: 10.4049/jimmunol.1202448
– volume: 2020
  ident: ppat.1009195.ref040
  article-title: Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP)
  publication-title: medRxiv
– volume: 25
  issue: 3
  year: 2020
  ident: ppat.1009195.ref050
  article-title: Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR
  publication-title: Euro Surveill
  doi: 10.2807/1560-7917.ES.2020.25.3.2000045
– volume: 33
  start-page: 1
  issue: 1
  year: 2005
  ident: ppat.1009195.ref043
  article-title: Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury
  publication-title: Crit Care Med
  doi: 10.1097/01.CCM.0000149854.61192.DC
– ident: ppat.1009195.ref054
– volume: 130
  start-page: 2620
  issue: 5
  year: 2020
  ident: ppat.1009195.ref024
  article-title: Clinical and immunological features of severe and moderate coronavirus disease 2019
  publication-title: J Clin Invest
  doi: 10.1172/JCI137244
– volume: 157
  start-page: 104833
  year: 2020
  ident: ppat.1009195.ref046
  article-title: Physiological and pathological regulation of ACE2, the SARS-CoV-2 receptor
  publication-title: Pharmacol Res
  doi: 10.1016/j.phrs.2020.104833
– volume: 41
  start-page: 1339
  issue: 6
  ident: ppat.1009195.ref006
  article-title: Rising evidence for neurological involvement in COVID-19 pandemic
  publication-title: Neurol Sci. 2020
– volume: 3
  start-page: 93
  issue: 1
  year: 2020
  ident: ppat.1009195.ref013
  article-title: Age-related rhesus macaque models of COVID-19
  publication-title: Animal Model Exp Med
  doi: 10.1002/ame2.12108
– year: 2020
  ident: ppat.1009195.ref018
  article-title: Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment
  publication-title: Cell
– volume: 579
  start-page: 270
  issue: 7798
  year: 2020
  ident: ppat.1009195.ref016
  article-title: A pneumonia outbreak associated with a new coronavirus of probable bat origin
  publication-title: Nature
  doi: 10.1038/s41586-020-2012-7
– volume: 7
  start-page: 1003
  issue: 6
  ident: ppat.1009195.ref039
  article-title: Elevated plasma levels of selective cytokines in COVID-19 patients reflect viral load and lung injury
  publication-title: National Science Review. 2020
  doi: 10.1093/nsr/nwaa037
– volume: 395
  start-page: 497
  issue: 10223
  year: 2020
  ident: ppat.1009195.ref026
  article-title: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
  publication-title: The Lancet
  doi: 10.1016/S0140-6736(20)30183-5
– year: 2020
  ident: ppat.1009195.ref020
  article-title: A Mouse Model of SARS-CoV-2 Infection and Pathogenesis
  publication-title: Cell Host Microbe
– volume: 5
  issue: 50
  year: 2020
  ident: ppat.1009195.ref028
  article-title: Natural killer cell immunotypes related to COVID-19 disease severity
  publication-title: Sci Immunol
  doi: 10.1126/sciimmunol.abd6832
– year: 2020
  ident: ppat.1009195.ref032
  article-title: Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2
  publication-title: Cell
– volume: 80
  start-page: 607
  issue: 6
  year: 2020
  ident: ppat.1009195.ref025
  article-title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19
  publication-title: J Infect
  doi: 10.1016/j.jinf.2020.03.037
– volume: 129
  start-page: 109147
  year: 2020
  ident: ppat.1009195.ref003
  article-title: Spectrum of chest computed tomographic (CT) findings in coronavirus disease-19 (COVID-19) patients in India
  publication-title: Eur J Radiol
  doi: 10.1016/j.ejrad.2020.109147
– volume: 2020
  ident: ppat.1009195.ref035
  article-title: Evaluation of K18-hACE2 mice as a model of SARS-CoV-2 infection
  publication-title: bioRxiv
– volume: 10
  start-page: e0124080
  issue: 4
  year: 2015
  ident: ppat.1009195.ref049
  article-title: Specific Depletion of Ly6Chi Inflammatory Monocytes Prevents Immunopathology in Experimental Cerebral Malaria
  publication-title: PLOS ONE
  doi: 10.1371/journal.pone.0124080
– year: 2020
  ident: ppat.1009195.ref008
  article-title: Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China
  publication-title: JAMA Neurol
– year: 2020
  ident: ppat.1009195.ref017
  article-title: Broad and differential animal ACE2 receptor usage by SARS-CoV-2
  publication-title: bioRxiv
– volume: 43
  start-page: E005
  issue: 0
  year: 2020
  ident: ppat.1009195.ref041
  article-title: [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]
  publication-title: Zhonghua Jie He He Hu Xi Za Zhi
– volume: 15
  start-page: 700
  issue: 5
  ident: ppat.1009195.ref036
  article-title: Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer
  publication-title: J Thorac Oncol. 2020
  doi: 10.1016/j.jtho.2020.02.010
– ident: ppat.1009195.ref001
– volume: 167
  start-page: 105951
  year: 2020
  ident: ppat.1009195.ref002
  article-title: Coronavirus Disease 2019-related dyspnea cases difficult to interpret using chest computed tomography
  publication-title: Respir Med
  doi: 10.1016/j.rmed.2020.105951
– volume: 100
  start-page: 1275
  issue: 5
  year: 2019
  ident: ppat.1009195.ref047
  article-title: Gamma Irradiation as an Effective Method for Inactivation of Emerging Viral Pathogens
  publication-title: The American journal of tropical medicine and hygiene
  doi: 10.4269/ajtmh.18-0937
– volume: 27
  start-page: 704
  issue: 5
  year: 2020
  ident: ppat.1009195.ref010
  article-title: Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
  publication-title: Cell Host Microbe
  doi: 10.1016/j.chom.2020.03.023
– year: 2020
  ident: ppat.1009195.ref012
  article-title: Establishment of an African green monkey model for COVID-19
  publication-title: bioRxiv
– volume: 2017
  start-page: 6104054
  year: 2017
  ident: ppat.1009195.ref023
  article-title: IL-10: A Multifunctional Cytokine in Viral Infections
  publication-title: J Immunol Res
  doi: 10.1155/2017/6104054
– ident: ppat.1009195.ref052
– volume: 5
  start-page: 562
  issue: 4
  year: 2020
  ident: ppat.1009195.ref015
  article-title: Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses
  publication-title: Nature microbiology
  doi: 10.1038/s41564-020-0688-y
– year: 2020
  ident: ppat.1009195.ref022
  article-title: A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures
  publication-title: bioRxiv
– year: 2020
  ident: ppat.1009195.ref031
  article-title: A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies
  publication-title: Cell
– volume: 2020
  ident: ppat.1009195.ref034
  article-title: Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease
  publication-title: bioRxiv
– volume: 323
  start-page: 2518
  issue: 24
  year: 2020
  ident: ppat.1009195.ref037
  article-title: Postmortem Examination of Patients With COVID-19
  publication-title: JAMA
  doi: 10.1001/jama.2020.8907
– volume: 35
  start-page: 1545
  issue: 5
  year: 2020
  ident: ppat.1009195.ref005
  article-title: Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19)
  publication-title: J Gen Intern Med
  doi: 10.1007/s11606-020-05762-w
– volume: 24
  start-page: 198
  issue: 1
  ident: ppat.1009195.ref004
  article-title: Acute respiratory failure in COVID-19: is it "typical" ARDS?
  publication-title: Crit Care. 2020
– volume: 146
  start-page: 119
  issue: 1
  ident: ppat.1009195.ref027
  article-title: Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19
  publication-title: J Allergy Clin Immunol
  doi: 10.1016/j.jaci.2020.04.027
– volume: 2020
  ident: ppat.1009195.ref038
  article-title: Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans
  publication-title: medRxiv
– volume: 26
  start-page: 711
  issue: 6
  year: 2008
  ident: ppat.1009195.ref042
  article-title: The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome
  publication-title: Am J Emerg Med
  doi: 10.1016/j.ajem.2007.10.031
– volume: 143
  start-page: 30
  year: 2017
  ident: ppat.1009195.ref051
  article-title: Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets
  publication-title: Antiviral Res
  doi: 10.1016/j.antiviral.2017.03.025
– year: 2019
  ident: ppat.1009195.ref053
  publication-title: Implementation of heatmaps that offers more control over dimensions and appearance
– year: 2020
  ident: ppat.1009195.ref007
  article-title: SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart
  publication-title: Heart Lung Circ
– year: 2020
  ident: ppat.1009195.ref033
  article-title: Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
  publication-title: bioRxiv
– volume: 11
  issue: 1206
  year: 2020
  ident: ppat.1009195.ref044
  article-title: Could SARS-CoV-2-Induced Hyperinflammation Magnify the Severity of Coronavirus Disease (CoViD-19) Leading to Acute Respiratory Distress Syndrome?
  publication-title: Frontiers in Immunology
– year: 2020
  ident: ppat.1009195.ref009
  article-title: Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility
  publication-title: Clin Infect Dis
– volume: 5
  start-page: e00362
  issue: 4
  year: 2020
  ident: ppat.1009195.ref029
  article-title: Clinical Characteristics and Immune Injury Mechanisms in 71 Patients with COVID-19
  publication-title: Msphere
– volume: 81
  start-page: 813
  issue: 2
  year: 2007
  ident: ppat.1009195.ref019
  article-title: Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus
  publication-title: J Virol
  doi: 10.1128/JVI.02012-06
– year: 2020
  ident: ppat.1009195.ref011
  article-title: Respiratory disease in rhesus macaques inoculated with SARS-CoV-2
  publication-title: Nature
– volume: 26
  start-page: 845
  issue: 6
  year: 2020
  ident: ppat.1009195.ref045
  article-title: Antibody responses to SARS-CoV-2 in patients with COVID-19
  publication-title: Nat Med
  doi: 10.1038/s41591-020-0897-1
– year: 2020
  ident: ppat.1009195.ref021
  article-title: Rapid adaption of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy
  publication-title: BioRxiv
– volume: 368
  start-page: 1012
  issue: 6494
  year: 2020
  ident: ppat.1009195.ref014
  article-title: Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model
  publication-title: Science
  doi: 10.1126/science.abb7314
– reference: 32803199 - bioRxiv. 2020 Aug 11:2020.08.11.246314. doi: 10.1101/2020.08.11.246314.
SSID ssj0041316
Score 2.6616552
Snippet SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the...
Expression of hACE2 is driven by a cytokeratin promoter in the airway epithelial cells as well as in epithelia of other internal organs, including the liver,...
SourceID plos
doaj
pubmedcentral
proquest
gale
pubmed
crossref
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
StartPage e1009195
SubjectTerms Alveoli
Angiotensin-Converting Enzyme 2 - genetics
Angiotensin-Converting Enzyme 2 - immunology
Animals
Antigens
Biology and life sciences
Coronaviruses
COVID-19
COVID-19 - genetics
COVID-19 - immunology
COVID-19 - pathology
COVID-19 - virology
Cytokeratin
Disease Models, Animal
Dose-response relationship (Biochemistry)
Edema
Engineering and Technology
Epithelial cells
Female
Fibrin
Gastrointestinal system
Gastrointestinal tract
Gene expression
Genomes
Health aspects
Humans
Hyperplasia
Immunoreactivity
Infections
Inflammation
Irradiated
Keratin-18 - genetics
Keratin-18 - immunology
Kidneys
Leukocytes (neutrophilic)
Lung - immunology
Lung - pathology
Lungs
Lymphocytes
Lymphocytes - immunology
Macrophages
Macrophages - immunology
Male
Medicine and health sciences
Mice
Mice, Transgenic
Necrosis
Neutrophils
Organs
Pathology
Pneumocytes
Pneumonia
Promoter Regions, Genetic
Promoters (Genetics)
Rectum
Research and Analysis Methods
Respiratory diseases
SARS-CoV-2 - physiology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Shedding
Trachea - immunology
Trachea - virology
Transgenic animals
Viral diseases
Viruses
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwELbQSkhcEOXVQEEBIXEyjWM7to_LslULokhAUW-W7XhbpJJd7ePQf89M4g0bVNQL13gcyePxzGfN-BtC3si6NnxmIq08wDekLKe-dJIic4jURsfC4QPnz6fV8Zn4eC7Pd1p9YU1YRw_cKe5QGe1iqZivihrJ6RxgEHAWDPNTdZhF9L4Q87aXqc4Hg2dum55iUxyqeFWlR3NcscO0R-8WC4f00TAXe0vsBKWWu7_30KPF1Xx1E_z8u4pyJywdPSD3E57Mx9069sid2Dwkd7sOk9ePyPQT0_RyPJmWOfadz9MbqXz5J8OepxwNfou_PD5PzyFcxmXMJ19-nHygzDwmZ0fT75Njmjon0AB4ZE3ryAJzEIfg-ieV46WW2jEIh94bJrA2r9JS1poHb2rGRYnJF6-F1N7xwnj-hIyaeRP3Se5rySonnSxCEMEUXgmNKNJEKSKrVUb4VnU2JFpx7G5xZdtcmYLrRacJiwq3SeEZof2sRUercYv8e9yVXhZJsdsPYCo2mYq9zVQy8hr31CLtRYN1NRdus1rZk2-ndoxAlWEO8Z9CXwdCb5PQbA6LDS69ZQCVIZ3WQPJgIAmHNwyG99G-tmteWbgNY98NAKIwc2tzNw-_6ofxp1gr18T5BmXAxwLOq1hGnnYm2uuNc1EBgtUZUQPjHSh2ONL8vGxZxxXebIV-9j924jm5V2JtUMHAhg_IaL3cxBcA7tb-ZXuOfwPRNEgh
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: Health & Medical Collection (Proquest)
  dbid: 7X7
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV1Lb9QwELZgERIXxLspBQWExMk0juPYOaFl2aoFUSSgaG-RX9sitUnY7B7498wk3rRBBa7xJErG43lkZr4h5JVwruDLwtPcgPuGkOXUpFpQRA4RqlA-0djg_Ok4PzzJPizEIvxwa0NZ5VYndora1Rb_ke9DmIADCcBCv21-UpwahdnVMELjJrmF0GUYfMnFEHCBfu5Gn-JoHCp5nofWOS7ZftipN02jEUQarCZOmLhimjoE_0FPT5rzur3OCf2zlvKKcTq4R-4GrzKe9mJwn9zw1QNyu58z-eshmX9kip5NZ_M0xunzceiUileXefY4ZGrwmr8w2KQeg9H0Kx_PPn8_ek9Z8YicHMy_zQ5pmJ9ALXgla-o8s0yDNYIgUEjNUyWUZmAUjSlYhhV6uRLCKW5N4RjPUkzBGJUJZTRPCsMfk0lVV36HxMYJlmuhRWJtZovEyEyhL1l4kXnmZET4lnWlDeDiOOPivOwyZhKCjJ4TJTK8DAyPCB3uanpwjf_Qv8NdGWgRGru7UK9Oy3DSSlko7VPJTJ44RDPU4LSCdWGY0HR26SPyEve0RPCLCqtrTvWmbcujr8flFN1VhpnEvxJ9GRG9DkTLGj7W6tDRACxDUK0R5d6IEo6wHS3voHxtv7ktL4Ud7tzK3PXLL4ZlfChWzFW-3iANaFrw9nIWkSe9iA584zzLwY9VEZEj4R0xdrxS_TjrsMclxreZ2v33az0ld1Ks_UkYSOcemaxXG_8MnLe1ed6d0N-9HT-B
  priority: 102
  providerName: ProQuest
Title K18-hACE2 mice develop respiratory disease resembling severe COVID-19
URI https://www.ncbi.nlm.nih.gov/pubmed/33465158
https://www.proquest.com/docview/2490315256
https://www.proquest.com/docview/2479419061
https://pubmed.ncbi.nlm.nih.gov/PMC7875348
https://doaj.org/article/798ae271b60d4475a045eac12954dcfe
http://dx.doi.org/10.1371/journal.ppat.1009195
Volume 17
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV3fb9MwELa2Tki8IH4vY1QBIfGUKU7i2H5AqCudNtAKGhT1LbITd5tUki5pJfbfc5c4gaAOXuNzJF_Ovs85-_sIecOyTIYLabxYA3xDynJPB4p5yBzChBTGV3jB-Xwan86ij3M23yGtZqt1YLV1a4d6UrNyefTz5vY9TPh3tWoDp22no9VKISE0ZEDJdske5CaOYg7nUVdXgBW7FkNFsRyPh3FsL9Pd9ZZesqo5_buVe7BaFtU2WPr36co_0tXJQ_LA4kx31ATGI7Jj8sfkXqM8efuETD5R4V2NxpPART16196dcsvflXfX1m7wmfmh8dq6C2nUlMYdf_5-9sGj8imZnUy-jU89q6jgpYBT1l5maEoV5CfYFjKuwkAwoSikSa0ljfDMXiwYy0SYapnRMAqwKKNFxIRWoS91-IwM8iI3-8TVGaOxYor5aRql0tc8EogupWGRoRl3SNi6Lkkt3TiqXiyTuobGYdvReCJBhyfW4Q7xul6rhm7jP_bH-FU6WyTLrh8U5WVi517CpVAm4FTHfob8hgpgLOQbiiXOLF0Yh7zGb5ogHUaO520u1aaqkrOv02SEAJZibfFOo4ue0VtrtChgsKmydxzAZUiz1bM87FnCpE57zfsYX-2YqwR2yajHAQAVerYxt735VdeML8UzdLkpNmgDay_gv5g65HkTop3fwjCKAdkKh_Be8PYc22_Jr69qNnKOO95IHPx7QC_I_QBPA_kUovOQDNblxrwEOLfWQ7LL53xI9o4n0y8Xw_qnyLCetb8A2Z5IjA
linkProvider Scholars Portal
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELbKVgguiHcXCgQE4hQax3HiHBDabrfaZdsFlbbqzdiOt63UJss-hPqn-I3MJM62QQVOvcaTKBmP55F5fIS85VmWsnFq_ViD-4Yjy30dKu7j5BAuUmEDhQ3Ou6O4fxB9PuJHK-RX3QuDZZW1TiwVdVYY_Ee-AWECAhKAhf40-eEjahRmV2sIjUoshvbiJ4Rss4-DLdjfd2G43dvv9n2HKuAbsNVzP7PUUAU6GkIjnigWCi4UBVOhdUojrFuLBeeZYEanGWVRiIkJLSIutGJBqhk89xZZjRi4Ci2yutkbfd2rdT9YhBJsFcF4_ITFsWvWYwndcLLxYTJROLYa7DRiWlwxhiVmwNIytCZnxew6t_fP6s0r5nD7Prnn_FivUwneA7Ji84fkdoVsefGI9IZU-Cedbi_0EO_ec71Z3vQys--53BBes-ca2-I9MNN2ar3ul8PBlk_Tx-TgRnj7hLTyIrdrxNMZp7HiigfGRCYNdBIJ9F5TyyNLs6RNWM06adw4c0TVOJNlji6BsKbihESGS8fwNvGXd02qcR7_od_EXVnS4jDu8kIxPZbubMskFcqGCdVxkOH8RAVuMtgziinUzIxtm7zBPZU4biPHep5jtZjN5ODbSHbQQaaYu_wr0V6D6L0jGhfwsUa5HgpgGY7xalCuNyhBaZjG8hrKV_3NM3l5vODOWuauX369XMaHYo1ebosF0oBuB_8ypm3ytBLRJd8Yi2LwnEWbJA3hbTC2uZKfnpTTzhOMqCPx7N-v9Yrc6e_v7sidwWj4nNwNsfIooCCp66Q1ny7sC3Ad5_qlO68e-X7TKuI3wDp83A
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELbKIhAXxLsLBQICcQobx3HsHBBa9qEuCwUBRXsLtuNtkdpk2YdQ_xq_jpnESRtU4NRrPImS8Xi-mcyLkGc8yxI2T6wfazDfsGW5r0PFfewcwmUibaCwwPn9Xry7H72d8dkW-VXXwmBaZa0TS0WdFQb_kffATcCBBIDQvblLi_g4HL9e_PBxghRGWutxGpWITO3JT3DfVq8mQ9jr52E4Hn0Z7PpuwoBvALfXfmapoQr0NbhJXCgWSi4VBdjQOqER5rDFkvNMMqOTjLIoxCCFlhGXWrEg0Qyee4lcFgxgE86SmDXOHmBDOXYVx_L4gsWxK9tjgvaclLxcLBQ2sAbExukWZ2CxnB7QYERncVSszjOA_8zjPAOM4xvkurNovX4lgjfJls1vkSvVjMuT22Q0pdI_7A9GoXcMSslzVVre8jTG77koEV6zxxoL5D0AbLu03uDD18nQp8kdsn8hnL1LOnmR223i6YzTWHHFA2MikwRaRBLt2MTyyNJMdAmrWZca19gc52scpWW0ToCDU3EiRYanjuFd4jd3LarGHv-hf4O70tBiW-7yQrE8SN0pT0UilQ0F1XGQYSdFBQYzIBvFYGpm5rZLnuKepth4I0cRPlCb1SqdfN5L-2gqU4xi_pXoU4vohSOaF_CxRrlqCmAZNvRqUe60KEF9mNbyNspX_c2r9PSgwZ21zJ2__KRZxoditl5uiw3SgJYHSzOmXXKvEtGGb4xFMdjQsktES3hbjG2v5N8Py77nAn3rSN7_92s9JldBMaTvJnvTB-RaiClIAQVB3SGd9XJjH4INudaPysPqkW8XrR1-A1j6f6w
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=K18-hACE2+mice+develop+respiratory+disease+resembling+severe+COVID-19&rft.jtitle=PLoS+pathogens&rft.au=Yinda%2C+Claude+Kwe&rft.au=Port%2C+Julia+R&rft.au=Bushmaker%2C+Trenton&rft.au=Offei+Owusu%2C+Irene&rft.date=2021-01-19&rft.pub=Public+Library+of+Science&rft.issn=1553-7366&rft.volume=17&rft.issue=1&rft_id=info:doi/10.1371%2Fjournal.ppat.1009195&rft.externalDocID=A650814582
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1553-7374&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1553-7374&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1553-7374&client=summon