Cited by 906SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research Studiesinterferon and immune responses

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SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function

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Winkler, Emma S., Bailey, Adam L., Kafai, Natasha M., Nair, Sharmila, McCune, Broc T., Yu, Jinsheng, Fox, Julie M., Chen, Rita E., Earnest, James T., Keeler, Shamus P., Ritter, Jon H., Kang, Liang-I, Dort, Sarah, Robichaud, Annette, Head, Richard, Holtzman, Michael J., Diamond, Michael S.·2020·Nature Immunology

DOI 10.1038/s41590-020-0778-2PMC PMC7578095

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Abstract

Although animal models have been evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, none have fully recapitulated the lung disease phenotypes seen in humans who have been hospitalized. Here, we evaluate transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lungs, with spread to other organs. A decline in pulmonary function occurs 4 days after peak viral titer and correlates with infiltration of monocytes, neutrophils and activated T cells. SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with signatures of nuclear factor-κB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures.

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Background
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Diagnostics of SARS-CoV-2 infection using electrical impedance spectroscopy with an immunosensor to detect the spike protein
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SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice
Stone, S., Rothan, H. A., Natekar, J. P., Kumari, P., Sharma, S., Pathak, H., Arora, K., Auroni, T. T., & Kumar, M. (2021) · Viruses · doi:10.3390/v14010027 · Cited by 33
Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice
Prompetchara, E., Ketloy, C., Alameh, M., Tharakhet, K., Kaewpang, P., Yostrerat, N., Pitakpolrat, P., Buranapraditkun, S., Manopwisedjaroen, S., Thitithanyanont, A., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37795-0 · Cited by 31
“K18-hACE2 transgenic mice are highly susceptible and displayed clinical signs following SARS-CoV-2 challenge 22,23 .”
The role of monocyte-derived macrophages in the lung: It’s all about context
T’Jonck, W., & Bain, C. C. (2023) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2023.106421 · Cited by 34
mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2
Hassert, M., Geerling, E., Stone, E. T., Steffen, T. L., Feldman, M. S., Dickson, A. M., Class, J., Richner, J. M., Brien, J. D., & Pinto, A. K. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1009163 · Cited by 30
“Allmost all of the mice that express hACE2 transgenically and transiently are on an H2 background, including the K18-hACE2 transgenic mouse model [32].”
Background
Experimental Models of SARS-CoV-2 Infection: Possible Platforms to Study COVID-19 Pathogenesis and Potential Treatments
Pandamooz, S., Jurek, B., Meinung, C.-P., Baharvand, Z., Shahem-abadi, A. S., Haerteis, S., Miyan, J. A., Downing, J. R., Dianatpour, M., Borhani‐Haghighi, A., et al. (2021) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-121120-012309 · Cited by 31
Therapeutic potential of melatonin and melatonergic drugs on K18‐hACE2 mice infected with SARS‐CoV‐2
Cecon, E., Izabelle, C., Poder, S. L., Real, F., Zhu, A., Tu, L., Ghigna, M., Klonjkowski, B., Bomsel, M., Jockers, R., et al. (2021) · Journal of Pineal Research · doi:10.1111/jpi.12772 · Cited by 33
Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics
Wyler, E., Adler, J. M., Eschke, K., Alves, G. T., Peidli, S., Pott, F., Kazmierski, J., Michalick, L., Kershaw, O., Bushe, J., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.03.014 · Cited by 33
“Therefore, we analyzed previously established viral-infectionrelated gene sets, response to type I interferon (IFN) and IFN-gamma (IFN-g).(28,29) In Syrian hamsters, the amplitude of the type I IFN response genes decreased from 5 to 7 dpi in the absence of treatment (Figures 2G and S2A).”
RIG-I-induced innate antiviral immunity protects mice from lethal SARS-CoV-2 infection
Marx, S., Kümmerer, B. M., Grützner, C., Kato, H., Schlee, M., Renn, M., Bartok, E., & Hartmann, G. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.02.008 · Cited by 35
Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SARS-CoV-2 infection
Kenney, D., O’Connell, A. K., Turcinovic, J., Montanaro, P., Hekman, R. M., Tamura, T., Berneshawi, A. R., Cafiero, T. R., Abdullatif, S. A., Blum, B. C., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110714 · Cited by 35
SARS-CoV-2 and its Multifaceted Impact on Bone Health: Mechanisms and Clinical Evidence
Harris, A., Creecy, A., Awosanya, O. D., McCune, T. R., Ozanne, M. V., Toepp, A. J., Kacena, M. A., & Qiao, X. (2024) · Current Osteoporosis Reports · doi:10.1007/s11914-023-00843-1 · Cited by 33
“Various models, including those using mice and golden Syrian hamsters, have been developed to mimic the human response to the virus [26–28].”
Method
SARS-CoV-2 viability under different meteorological conditions, surfaces, fluids and transmission between animals
Fernández‐Raga, M., Díaz-Marugán, L., Escolano, M. G., Bort, C., & Fanjul, V. (2020) · Environmental Research · doi:10.1016/j.envres.2020.110293 · Cited by 29
The Delta SARS-CoV-2 Variant of Concern Induces Distinct Pathogenic Patterns of Respiratory Disease in K18-hACE2 Transgenic Mice Compared to the Ancestral Strain from Wuhan
Liu, X., Mostafavi, H., Ng, W. H., Freitas, J. R., King, N. J. C., Zaid, A., Taylor, A., & Mahalingam, S. (2022) · mBio · doi:10.1128/mbio.00683-22 · Cited by 31
Protective non-neutralizing SARS-CoV-2 monoclonal antibodies
Izadi, A., & Nordenfelt, P. (2024) · Trends in Immunology · doi:10.1016/j.it.2024.06.003 · Cited by 36
Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection
Elia, U., Rotem, S., Bar‐Haim, E., Ramishetti, S., Naidu, G. S., Gur, D., Aftalion, M., Israeli, M., Bercovich-Kinori, A., Alcalay, R., et al. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c01284 · Cited by 30
ATP/IL‐33‐triggered hyperactivation of mast cells results in an amplified production of pro‐inflammatory cytokines and eicosanoids
Jordan, P. M., Andreas, N., Groth, M., Wegner, P., Weber, F., Jäger, U., Küchler, C., Werz, O., Serfling, E., Kamradt, T., et al. (2021) · Immunology · doi:10.1111/imm.13386 · Cited by 31
Attenuated activation of pulmonary immune cells in mRNA-1273–vaccinated hamsters after SARS-CoV-2 infection
Meyer, M., Wang, Y., Edwards, D. K., Smith, G. R., Rubenstein, A. B., Ramanathan, P., Mire, C. E., Pietzsch, C. A., Chen, X., Ge, Y., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148036 · Cited by 43
Rapid Development of Analytical Methods for Evaluating Pandemic Vaccines: A Covid-19 Perspective
Baldwin, J., Piplani, S., Sakala, I. G., Honda‐Okubo, Y., Li, L., & Petrovsky, N. (2021) · Bioanalysis · doi:10.4155/bio-2021-0096 · Cited by 33
“hACE2 mice have similarly been shown to be suitable for SARS-CoV-2 infection [132,139,140].”
Background
Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting
Hauser, B. M., Sangesland, M., Denis, K. S., Lam, E. C., Case, J. B., Windsor, I. W., Feldman, J. E., Caradonna, T. M., Kannegieter, T., Diamond, M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110561 · Cited by 38
Self-citation
Antibody escape and global spread of SARS-CoV-2 lineage A.27
Kaleta, T., Kern, L., Hong, S. L., Hölzer, M., Kochs, G., Beer, J., Schnepf, D., Schwemmle, M., Bollen, N., Kolb, P., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28766-y · Cited by 33
Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression
Bishop, C., Dumenil, T. D., Rawle, D. J., Le, T. T., Yan, K., Tang, B., Härtel, G., & Suhrbier, A. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010867 · Cited by 28
“The high viral read counts in K18-hACE2 mice was perhaps not surprising given that this is a robust lethal model of SARS-CoV-2 infection [20, 30, 40].”
BackgroundMethod
DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2
Parzych, E. M., Du, J., Ali, A., Schultheis, K., Frase, D. M., Smith, T. R. F., Cui, J., Chokkalingam, N., Tursi, N. J., Andrade, V. M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33309-6 · Cited by 30
SARS CoV-2 infections in animals, two years into the pandemic
Frazzini, S., Amadori, M., Turin, L., & Riva, F. (2022) · Archives of Virology · doi:10.1007/s00705-022-05609-1 · Cited by 31
Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses
Nath, P., Chauhan, N. R., Jena, K. K., Datey, A., Kumar, N. D., Mehto, S., De, S., Nayak, T. K., Priyadarsini, S., Rout, K., et al. (2021) · EMBO Reports · doi:10.15252/embr.202152948 · Cited by 31
“A robust induction of type I IFN response upon SARS-CoV-2 infection is reported (Winkler et al , 2020; Zhou et al , 2020).”
Interferon-Lambda Intranasal Protection and Differential Sex Pathology in a Murine Model of SARS-CoV-2 Infection
Sohn, S.-Y., Hearing, J., Mugavero, J., Kirillov, V., Gorbunova, E., Helminiak, L., Mishra, S., Mackow, E. R., Hearing, P., Reich, N. C., et al. (2021) · mBio · doi:10.1128/mbio.02756-21 · Cited by 28
“by the cytokeratin-18 promoter (K18-hACE2) (33, 34).”
Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice
Bi, Z., Hong, W., Que, H., He, C., Ren, W., Yang, J., Lu, T., Chen, L., Lu, S., Peng, X., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00851-6 · Cited by 30
“The result was almost consistent with the clinical course of ARDS patients(18,19) and other severe models of hACE2 mice infected by SARS-CoV-2 or mice infected by mouse adapted SARS-CoV-2.(8,20,21)”
ResultInfluential
A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection
Pérez, P., Lázaro-Frías, A., Zamora, C., Sánchez‐Cordón, P. J., Astorgano, D., Luczkowiak, J., Delgado, R. B., Casasnovas, J. M., Estéban, M., & García‐Arriaza, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.824728 · Cited by 30
“As we observed that one single dose of MVA-S(3P) was more immunogenic than one dose of MVA-S in C57BL/6 mice, we next evaluated the efficacy triggered by one dose of both vaccine candidates in transgenic K18-hACE2 mice, susceptible to SARSCoV-2 infection (31, 32).”
Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice
Lázaro-Frías, A., Pérez, P., Zamora, C., Sánchez‐Cordón, P. J., Guzmán, M. G., Luczkowiak, J., Delgado, R. B., Casasnovas, J. M., Estéban, M., & García‐Arriaza, J. (2022) · npj Vaccines · doi:10.1038/s41541-022-00440-w · Cited by 30
Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants
Wang, Y., Yan, A., Song, D., Duan, M., Dong, C., Chen, J., Jiang, Z., Gao, Y., Rao, M., Feng, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45050-3 · Cited by 29
Progress in Research on Inhibitors Targeting SARS-CoV-2 Main Protease (M pro )
Yang, Y., Luo, Y., Zhang, C., Xiang, Y., Bai, X., Zhang, D., Fu, Z., Hao, R.-B., & Liu, X. (2024) · ACS Omega · doi:10.1021/acsomega.4c03023 · Cited by 34
Exploring the utility of extracellular vesicles in ameliorating viral infection-associated inflammation, cytokine storm and tissue damage
Pillalamarri, N., Abdullah, A., Ren, G., Khan, L., Ullah, A., Jonnakuti, S. T., & Ullah, M. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101095 · Cited by 29
“Understanding the role of ACE2, and the use of small extracellular vesicles to deliver ACE2 to targeted tissues, may even prevent future outbreaks of coronaviruses [ 57 , 58 ].”
In Vivo protection from SARS-CoV-2 infection by ATN-161 in k18-hACE2 transgenic mice
Amruta, N., Engler-Chiurazzi, E. B., Murray-Brown, I. C., Gressett, T. E., Biose, I. J., Chastain, W. H., Befeler, J. B., & Bix, G. J. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119881 · Cited by 29
“Cxcl10 mRNA expression was significantly upregulated in the lungs of SARS-CoV-2 infected mice as has previously been reported [50].”
Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models
Sheward, D. J., Mandolesi, M., Urgard, E., Kim, C., Hanke, L., Vidakovics, L. P., Pankow, A. P., Smith, N. L., Dopico, X. C., McInerney, G. M., et al. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100450 · Cited by 28
Progression and Resolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Golden Syrian Hamsters
Mulka, K. R., Beck, S., Solis, C. V., Johanson, A. L., Queen, S., McCarron, M. E., Richardson, M., Zhou, R., Marinho, P., Jedlicka, A., et al. (2021) · American Journal of Pathology · doi:10.1016/j.ajpath.2021.10.009 · Cited by 27
Biparatopic nanobodies protect mice from lethal challenge with SARS‐CoV‐2 variants of concern
Wagner, T. R., Schnepf, D., Beer, J., Klingel, K., Ruetalo, N., Kaiser, P. D., Junker, D., Sauter, M., Traenkle, B., Frecot, D. I., et al. (2021) · EMBO Reports · doi:10.15252/embr.202153865 · Cited by 27
“To evaluate their protective efficacy in vivo , transgenic mice expressing human ACE2 (K18-hACE2 mice) (McCray et al , 2007; Winkler et al , 2020) were challenged with a lethal dose of the early circulating SARS-CoV-2 B.1, VOC B.1.351 (Beta) or VOC B.1.617.2 (Delta).”
Influential
Nanobodies Protecting From Lethal SARS-CoV-2 Infection Target Receptor Binding Epitopes Preserved in Virus Variants Other Than Omicron
Casasnovas, J. M., Margolles, Y., Noriega, M. A., Guzmán, M. Á., Arranz, R., Melero, R., Casanova, M., Sánchez, J. A. C., de Oya, N. J., Gastaminza, P., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.863831 · Cited by 30
“We performed a post-exposure protection assay in K18-hACE2 transgenic mice that reproduce major clinical symptoms of COVID-19 in humans (56).”
Method
Spike protein-independent attenuation of SARS-CoV-2 Omicron variant in laboratory mice
Liu, S., Selvaraj, P., Sangare, K., Luan, B., & Wang, T. T. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111359 · Cited by 29
Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output
Rommel, M. G. E., Walz, L., Fotopoulou, F., Kohlscheen, S., Schenk, F., Miskey, C., Botezatu, L., Krebs, Y., Voelker, I. M., Wittwer, K., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111447 · Cited by 29
Severe acute respiratory disease in American mink experimentally infected with SARS-CoV-2
Adney, D. R., Lovaglio, J., Schulz, J. E., Yinda, C. K., Avanzato, V. A., Haddock, E., Port, J. R., Holbrook, M. G., Hanley, P. W., Saturday, G. A., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.159573 · Cited by 29
“Progression into severe disease is typically presented as worsening respiratory disease, hypoxemia, and radiographic lesions, with endpoint markers that can include coagulopathies, thromboembolism, acute kidney injury, and ARDS (22–25).”
BackgroundMethodInfluential
SARS-CoV-2 infection dysregulates NAD metabolism
Izadpanah, A., Mudd, J. C., Garcia, J. G. N., Srivastav, S., Abdel‐Mohsen, M., Palmer, C. S., Goldman, A. R., Kolls, J. K., Qin, X., & Rappaport, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1158455 · Cited by 29
“We also mined data from another group using a similar K18-hACE2 model of SARS-CoV-2 infection and found a time-dependent increase in Nampt levels in lungs (30) (Figure 2E) (GSE154104).”
Method
Severe acute respiratory syndrome coronavirus 2 infection leads to Tau pathological signature in neurons
Primio, C. D., Quaranta, P., Mignanelli, M., Siano, G., Bimbati, M., Scarlatti, A., Piazza, C. R., Spezia, P. G., Perrera, P., Basolo, F., et al. (2023) · PNAS Nexus · doi:10.1093/pnasnexus/pgad282 · Cited by 29
“Given our findings in neuron-like cells, we assessed Tau modulation in vivo by challenging a transgenic mouse line expressing human ACE2 (K18-hACE2 ) model ( 43) with the SARS-CoV-2 B.1 viral strain.”
High-Fat High-Sugar Diet-Induced Changes in the Lipid Metabolism Are Associated with Mildly Increased COVID-19 Severity and Delayed Recovery in the Syrian Hamster
Port, J. R., Adney, D. R., Schwarz, B. H., Schulz, J. E., Sturdevant, D. E., Smith, B. J., Avanzato, V. A., Holbrook, M. G., Purushotham, J. N., Stromberg, K. A., et al. (2021) · Viruses · doi:10.3390/v13122506 · Cited by 28
“Previously, lung function analysis after SARS-CoV-2 infection in a rodent model has only been demonstrated in ACE2 mice [37].”
Background
Identification of potent inhibitors of SARS-CoV-2 infection by combined pharmacological evaluation and cellular network prioritization
Patten, J. J., Keiser, P. T., Gysi, D. M., Menichetti, G., Mori, H., Donahue, C. J., Gan, X., do Valle, Í. F., Geoghegan-Barek, K. M., Anantpadma, M., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104925 · Cited by 28
Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection
Pérez, P., Astorgano, D., Albericio, G., Flores, S., Sánchez‐Cordón, P. J., Luczkowiak, J., Delgado, R. B., Casasnovas, J. M., Estéban, M., & García‐Arriaza, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.995235 · Cited by 30
Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity
Alturaiki, W., Alkadi, H. S., Alamri, S. S., Awadalla, M., Alfaez, A., Mubarak, A., Alanazi, M. A., Alenzi, F. Q., Flanagan, B., & Alosaimi, B. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e12653 · Cited by 28
Microvascular significance of TGF-β axis activation in COVID-19
Arguinchona, L., Zagona‐Prizio, C., Joyce, M. E., Chan, E. D., & Maloney, J. P. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1054690 · Cited by 30
Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV ‐2‐related mortality in mice
Pastor‐Fernández, A., Bertos, A. R., Sierra‐Ramírez, A., del Moral‐Salmoral, J., Merino, J., de Ávila, A. I., Olagüe, C., Villares, R., González‐Aseguinolaza, G., Rodríguez, M. Á., et al. (2023) · Aging Cell · doi:10.1111/acel.13771 · Cited by 28

Authors: Winkler, E. S., Bailey, A. L., Kafai, N. M., Nair, S., McCune, B. T., Yu, J., Fox, J. M., Chen, R. E., Earnest, J. T., Keeler, S. P., Ritter, J. H., Kang, L.-I., Dort, S., Robichaud, A., Head, R., Holtzman, M. J., & Diamond, M. S.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Diamond, Michael S.
ORCID: Winkler, Emma S.
Bailey, Adam L.
Kafai, Natasha M.
Nair, Sharmila
McCune, Broc T.
Yu, Jinsheng
Fox, Julie M.
Chen, Rita E.
Earnest, James T.
Keeler, Shamus P.
Ritter, Jon H.
Kang, Liang-I
Head, Richard
Holtzman, Michael J.
Diamond, Michael S.
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2020-08-24
Volume: 21
Issue: 11
Pages: 1327-1335
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/s41590-020-0778-2
PMC: PMC7578095
OpenAlex: W3080378920
Cited by: 901
References: 56
Citations by year: 2026: 55 · 2025: 72 · 2024: 124 · 2023: 131 · 2022: 234 · 2021: 252 · 2020: 32
FWCI: 21.20
Type: journal article
Language: en
Update notices: correction (2020-09-02)
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (75N93019C00062, R01 AI127828, R01 AI130591, R35 HL145242, F32 AI138392)
United States Department of Defense | Defense Advanced Research Projects Agency (HR001117S0019)
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords: SARS-CoV-2, COVID-19 pandemic, K18-hACE2 mice, animal model of COVID-19, lung inflammation, lung function decline, monocytes, neutrophils, T cell activation, innate immune response, interferon signaling, NF-κB signaling
MeSH terms: Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Chlorocebus aethiops, Disease Models, Animal, Female, Humans, Immunity, Innate, Interferon Type I, Interferon-gamma, Peptidyl-Dipeptidase A, Leukocytes, Lymphocyte Activation, Male, Mice, Transgenic, Monocytes, Neutrophils, Pneumonia, Pneumonia, Viral, Promoter Regions, Genetic, T-Lymphocytes, Vero Cells, Virus Replication, NF-kappa B, Coronavirus Infections, Neutrophil Infiltration, Mice, Keratin-18, Pandemics

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SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function

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