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
Quantitative proteomics and biological activity of extracellular vesicles engineered to express SARS‐CoV‐2 spike protein
Choi, D., Khan, N., Montermini, L., Tawil, N., Meehan, B., Kim, D., Roth, F. P., Divangahi, M., & Rak, J. W. (2022) · Journal of Extracellular Biology · doi:10.1002/jex2.58 · Cited by 15
“These transgenicmice express humanACE2 receptor and are susceptible to SARS-CoV-2 infection (Winkler et al., 2020).”
Background
Western diet increases COVID-19 disease severity in the Syrian hamsterPreprint
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) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.17.448814 · Cited by 14
An orally available Mpro/TMPRSS2 bispecific inhibitor with potent anti-coronavirus efficacy in vivo
Shuai, H., Qiao, J., Yoon, C., Zhang, G., Hou, Y., Xia, X., Wang, L., Deng, X., Wang, Y., Li, Q., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60832-z · Cited by 14
“We next proceeded to investigate the in vivo antiviral potency of TMP1usingtheK18humanACE2(K18-hACE2)transgenicmice,whichisa well-established infection model for COVID-19 research 41 – 43 .”
RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge
Wong, T. Y., Russ, B. P., Lee, K. S., Miller, O. A., Kang, J. H., Cooper, M., Winters, M. T., Rodriguez‐Aponte, S. A., Dalvie, N. C., Johnston, R. S., et al. (2022) · mSphere · doi:10.1128/msphere.00243-22 · Cited by 12
Lung T cell response in COVID-19
Shakiba, M. H., Gemünd, I. D., Beyer, M., & Bonaguro, L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1108716 · Cited by 13
“CoV-2 phenotype seen in the lung of humans, upregulation of T cell associated and pro-inflammatory cytokines was observed in the lung of SARS-CoV-2 infected K18-hACE2 transgenic mice (expressing the human angiotensin I converting enzyme 2 (ACE2) receptor) (48).”
Background
Inhibition of Toll-like receptor 4 and Interleukin-1 receptor prevent SARS-CoV-2 mediated kidney injury
Nakazawa, D., Takeda, Y., Kanda, M., Tomaru, U., Ogawa, H. K., Kudo, T., Shiratori‐Aso, S., Watanabe‐Kusunoki, K., Ueda, Y., Miyoshi, A., et al. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01584-x · Cited by 14
“ACE2-humanized mice develop renal tubular injury after SARS-CoV-2 infection [32], thus in vivo studies are required to evaluate the efficacy of these targets in the future.”
Background
An mRNA vaccine encoding the SARS-CoV-2 receptor-binding domain protects mice from various Omicron variants
Uraki, R., Imai, M., Ito, M., Yamayoshi, S., Kiso, M., Jounai, N., Miyaji, K., Iwatsuki‐Horimoto, K., Takeshita, F., & Kawaoka, Y. (2024) · npj Vaccines · doi:10.1038/s41541-023-00800-0 · Cited by 14
Immunoglobulin replacement products protect against SARS-CoV-2 infection in vivo despite poor neutralizing activity
Zimmerman, O., Doss, A. M. A., Ying, B., Liang, C.-Y., Mackin, S., Davis-Adams, H. G., Adams, L. J., VanBlargan, L. A., Chen, R. E., Scheaffer, S. M., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.176359 · Cited by 13
Self-citation
Pathogenesis and virulence of coronavirus disease: Comparative pathology of animal models for COVID-19
Kirk, N. M., Liang, Y., & Ly, H. (2024) · Virulence · doi:10.1080/21505594.2024.2316438 · Cited by 13
“Hematologic and coagulation abnormalities that occur in human disease have been documented in only a few of the animal models available thus far [122,169,196,202,244], although these readouts are generally not included in most studies.”
Background
Modulating the immune response to SARS-CoV-2 by different nanocarriers delivering an mRNA expressing trimeric RBD of the spike protein: COVARNA Consortium
Marcos-Villar, L., Perdiguero, B., Anthiya, S., Borrajo, M. L., Lou, G., Franceschini, L., Esteban, I., Sánchez‐Cordón, P. J., Zamora, C., Sorzano, C. Ó. S., et al. (2024) · npj Vaccines · doi:10.1038/s41541-024-00838-8 · Cited by 11
Recombinant OC43 SARS-CoV-2 spike replacement virus: An improved BSL-2 proxy virus for SARS-CoV-2 neutralization assays
Hu, Z., López-Muñoz, A. D., Košík, I., Li, T., Callahan, V., Brooks, K., Yee, D. S., Hollý, J., Santos, J. J. D. S., Brant, A. C., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2310421121 · Cited by 11
“We next examined the pathogenicity of rOC43 - CoV2 S in established mouse models of SARS - CoV - 2 and hOC43, using, respectively, transgenic hACE2 mice and WT neonatal C57BL/6 mice (older mice do not support OC43 infection) (18–21).”
MethodSelf-citation
SARS-CoV-2 infection in microglia and its sequelae: What do we know so far?
Luo, E. Y., Chang, R. C., & Gilbert‐Jaramillo, J. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100888 · Cited by 14
Abnormal Blood Coagulation and Kidney Damage in Aged Hamsters Infected with Severe Acute Respiratory Syndrome Coronavirus 2
Ohno, M., Sasaki, M., Orba, Y., Sekiya, T., Masum, M. A., Ichii, O., Sawamura, T., Kakino, A., Suzuki, Y., Kida, H., et al. (2021) · Viruses · doi:10.3390/v13112137 · Cited by 13
Spike Protein of SARS‐CoV‐2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice
Cao, X., Tian, Y., Nguyen, V., Zhang, Y., Gao, C., Yin, R. L., Carver, W., Fan, D., Albrecht, H., Cui, T., et al. (2021) · The FASEB Journal · doi:10.1096/fasebj.2021.35.s1.00265 · Cited by 13
Ronapreve (REGN-CoV; casirivimab and imdevimab) reduces the viral burden and alters the pulmonary response to the SARS-CoV-2 Delta variant (B.1.617.2) in K18-hACE2 mice using an experimental design reflective of a treatment use case
Tatham, L. M., Kipar, A., Sharp, J., Kijak, E., Herriott, J., Neary, M., Box, H., Toledo, E. G., Valentijn, A., Cox, H., et al. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.03916-23 · Cited by 13
“4) as previously described (36–38).”
3D Bioprinted Neural‐Like Tissue as a Platform to Study Neurotropism of Mouse‐Adapted SARS‐CoV‐2
de Melo, B. A. G., Mundim, M. V., Lemes, R. M. R., Cruz, E. M., Ribeiro, T. N., Santiago, C. F., da Fonsêca, J. H. L., Benincasa, J. C., Stilhano, R. S., Mantovani, N., et al. (2022) · Advanced Biology · doi:10.1002/adbi.202200002 · Cited by 14
Host chitinase 3-like-1 is a universal therapeutic target for SARS-CoV-2 viral variants in COVID-19
Kamle, S., Ma, B., Lee, C. M., Schor, G., Zhou, Y., Lee, C. G., & Elias, J. A. (2022) · eLife · doi:10.7554/elife.78273 · Cited by 13
Intranasal soluble ACE2 improves survival and prevents brain SARS-CoV-2 infection
Hassler, L., Wysocki, J. A., Ahrendsen, J. T., Ye, M., Gelarden, I. A., Nicolaescu, V. I., Τοματσίδου, Α., Gula, H., Cianfarini, C. L., Khurram, N., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202301969 · Cited by 14
Can GPR4 Be a Potential Therapeutic Target for COVID-19?
Yang, L. V., Oppelt, K. A., Thomassen, M. J., Marie, M. A., Akhtar, S. N., & McCallen, J. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2020.626796 · Cited by 15
Ketogenesis restrains aging-induced exacerbation of COVID in a mouse modelPreprint
Ryu, S., Shchukina, I., Youm, Y., Qing, H., Hilliard, B. K., Dlugos, T., Zhang, X., Yasumoto, Y., Booth, C. J., Fernandez-Hernando, C. F., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.11.294363 · Cited by 13
“For example, epithelial cell specific induction of hACE2 (K18-hACE2) as a model of SARS-CoV-2 infection demonstrated that post intranasal inoculation, animals develop lung inflammation and pneumonia driven by infiltration of monocytes, neutrophils and T cells (Winkler et al., 2020).”
Background
Severity of SARS-CoV-2 infection as a function of the interferon landscape across the respiratory tract of COVID-19 patientsPreprint
Sposito, B., Broggi, A., Pandolfi, L., Crotta, S., Ferrarese, R., Sisti, S., Clementi, N., Ambrosi, A., Liu, E., Frangipane, V., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.30.437173 · Cited by 13
Immunological and Pathological Peculiarity of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant
Lee, S.-H., Yoon, G. Y., Lee, S. J., Kwon, Y., Moon, H.-W., Kim, Y., Kim, H., Lee, W., Jeong, G. U., Kim, C., et al. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.02371-22 · Cited by 12
Enhanced virulence and waning vaccine-elicited antibodies account for breakthrough infections caused by SARS-CoV-2 delta and beyond
Kwon, H., Košíková, M., Tang, W., Ortega‐Rodriguez, U., Radvák, P., Xiang, R., Mercer, K. E., Muskhelishvili, L., Davis, K., Ward, J. M., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105507 · Cited by 11
TNF/iNOS/NO pathway mediates host susceptibility to endothelial-dependent circulatory failure and death induced by betacoronavirus infection
Vieira-Alves, I., Alves, A. R. P., Souza, N. M. V., de Melo, T. L., Coimbra-Campos, L. M. C., Lacerda, L. D. S. B., Queiroz‐Junior, C. M., Andrade, A. C. D. S. P., Barcelos, L. S., Teixeira, M. M., et al. (2023) · Clinical Science · doi:10.1042/cs20220663 · Cited by 12
Multiantigen pan-sarbecovirus DNA vaccines generate protective T cell immune responses
van Bergen, J., Camps, M. G. M., Pardieck, I. N., Veerkamp, D. M. B., Leung, W. Y., Leijs, A. A., Myeni, S. K., Kikkert, M., Arens, R., Zondag, G. C. M., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.172488 · Cited by 11
A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection
Coria, L. M., Rodriguez, J. M., Demaría, A., Bruno, L. A., Medrano, M. R., Castro, C. P., Castro, E. F., Priore, S. A. D., Hernando-Insúa, A., Kaufmann, I. G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45180-8 · Cited by 11
Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao, T., Kim, J., Peña-Hernández, M. A., Valle, G., Moriyama, M., Luyten, S., Ott, I. M., Gomez-Calvo, M. L., Gehlhausen, J. R., Baker, E., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2319566121 · Cited by 12
“In this model, the expression of human angiotensin - converting enzyme 2 (hACE2) is under the control of a keratin 18 (K18) gene promoter, enabling epithelial infection by SARS - CoV - 2 (14, 15).”
Background
SARS‐CoV‐2 infection induces thymic atrophy mediated by IFN‐γ in hACE2 transgenic mice
Rizvi, Z. A., Sadhu, S., Dandotiya, J., Sharma, P., Binayke, A., Singh, V., Das, V., Khatri, R., Kumar, R., Samal, S., et al. (2024) · European Journal of Immunology · doi:10.1002/eji.202350624 · Cited by 14
Influence of Th1 versus Th2 immune bias on viral, pathological, and immunological dynamics in SARS-CoV-2 variant-infected human ACE2 knock-in mice
Verma, S. K., Ana‐Sosa‐Batiz, F., Timis, J., Shafee, N., Maule, E., Pinto, P. B. A., Conner, C., Valentine, K. M., Cowley, D. O., Miller, R., et al. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105361 · Cited by 15
Intranasal liposomal angiotensin-(1-7) administration reduces inflammation and viral load in the lungs during SARS-CoV-2 infection in K18-hACE2 transgenic mice
Mendes, S., Guimarães, L. C., Costa, P. A. C., Fernandéz, C. C., Figueiredo, M. M., Teixeira, M. M., Santos, R. A. S., Guimarães, P. P. G., & Frézard, F. (2024) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00835-24 · Cited by 12
“K18-hACE2 mice infected with SARS-CoV-2 were used as a preclinical model of COVID-19, as described previously (29, 30).”
SIRT2 suppresses aging-associated cGAS activation and protects aged mice from severe COVID-19
Barthez, M., Xue, B., Zheng, J., Wang, Y., Song, Z., Mu, W., Wang, C.-L., Guo, J., Yang, F., Ma, Y., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115562 · Cited by 14
Fc-Independent Protection from SARS-CoV-2 Infection by Recombinant Human Monoclonal Antibodies
Noy-Porat, T., Edri, A., Alcalay, R., Makdasi, E., Gur, D., Aftalion, M., Evgy, Y., Beth-Din, A., Levy, Y., Epstein, E., et al. (2021) · Antibodies · doi:10.3390/antib10040045 · Cited by 10
“It was previously shown that SARS-CoV-2 infection of K18-hACE2 mice manifests as progressive and widespread viral pneumonia with perivascular and pan-alveolar inflammation, immune cell infiltration, edema, lung consolidation and distinctive vascular system injury that were apparent even three weeks after infection (in…”
Background
COVID-19 and cancer: start the resolution!
Barksdale, C., Kipper, F. C., Tripathy, S., Subbian, S., Serhan, C. N., & Panigrahy, D. (2022) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-10017-z · Cited by 14
A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant
Hingankar, N. K., Deshpande, S., Das, P., Rizvi, Z. A., Wibmer, C. K., Mashilo, P., Ansari, M. Y., Burns, A., Barman, S., Zhao, F., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010465 · Cited by 14
Animal Models to Test SARS-CoV-2 Vaccines: Which Ones Are in Use and Future Expectations
Lima, G. G., Portilho, A. I., & Gaspari, E. D. (2022) · Pathogens · doi:10.3390/pathogens12010020 · Cited by 13
Prophylaxis and treatment of SARS-CoV-2 infection by an ACE2 receptor decoy in a preclinical animal model
Tada, T., Dcosta, B. M., Zhou, H., & Landau, N. R. (2023) · iScience · doi:10.1016/j.isci.2023.106092 · Cited by 9
A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8
Rodriguez-Rodriguez, B. A., Ciabattoni, G. O., Duerr, R., Valero-Jimenez, A. M., Yeung, S. T., Crosse, K. M., Schinlever, A. R., Bernard, L., Galvan, J. R., McGrath, M. E., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38783-0 · Cited by 12
“Another limitation of our model is that the expression of the hACE2 transgene is driven by a non-native K18 promoter,allowingtheinfectionofmultipleorgans,andresultingintissue expression levels that are distinct from endogenously expressed murine Ace2 49,50 .”
Experimental Models for SARS-CoV-2 Infection
Kim, T., Lee, J. S., & Ju, Y. S. (2021) · Molecules and Cells · doi:10.14348/molcells.2021.0094 · Cited by 13
Review of selected animal models for respiratory coronavirus infection and its application in drug research
Qin, S., Li, R., Zheng, Z., Zeng, X., Wang, Y., & Wang, X. (2022) · Journal of Medical Virology · doi:10.1002/jmv.27718 · Cited by 11
SARS-CoV-2 Spike Protein Expression In Vitro and Hematologic Effects in Mice Vaccinated With AZD1222 (ChAdOx1 nCoV-19)
Stebbings, R., Jones, C. R., Cotton, P., Armour, G., Maguire, S., Skellett, V., Tang, C.-M., Goodman, J., Brady, T. M., Takahashi, V., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.836492 · Cited by 12
mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challengePreprint
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) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.25.428136 · Cited by 12
Neuroinvasion and neurotropism by SARS-CoV-2 variants in the K18-hACE2 mousePreprint
Seehusen, F., Clark, J. J., Sharma, P., Bentley, E. G., Kirby, A., Subramaniam, K. S., Wunderlin, S., Hughes, G. L., Patterson, E. I., Michael, B. D., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.16.440173 · Cited by 12
Evolutionary pathways to SARS-CoV-2 resistance are opened and closed by epistasis acting on ACE2
Castiglione, G. M., Zhou, L., Xu, Z., Neiman, Z. M., Hung, C., & Duh, E. J. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3001510 · Cited by 9
SARS-CoV-2 bivalent mRNA vaccine with broad protection against variants of concern
Ma, Q., Li, M., Ma, L., Zhang, C., Zhang, H., Zhong, H., Wen, J., Wang, Y., Yan, Z., Xiong, W., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1195299 · Cited by 11
“To compare the protective effect of RBMRNA-405 with monovalent RBMRNA-404, groups of 6- to 9-week-old K18hACE2 transgenic mice (n = 5 per group) (41) were immunized with 5 or 20 mg of RBMRNA-405 or RBMRNA-404 via intramuscular inject ions and boosted with ident ica l immunizations 3 weeks later.”
Method
The Immunomodulatory Role of Cell-Free Approaches in SARS-CoV-2-Induced Cytokine Storm—A Powerful Therapeutic Tool for COVID-19 Patients
Csöbönyeiová, M., Smolinská, V., Harsányi, Š., Ivantysyn, M., & Klein, M. (2023) · Biomedicines · doi:10.3390/biomedicines11061736 · Cited by 11
“Exosomes can enhance drug stability, bioavailability, and targeted delivery, potentially improving their efficacy and reducing side effects [162,163].”
Background
Generation and characterization of a humanized ACE2 mouse model to study long‐term impacts of SARS‐CoV‐2 infection
Choi, C., Gadhave, K., Villano, J., Pekosz, A. S., Mao, X., & Jia, H. (2024) · Journal of Medical Virology · doi:10.1002/jmv.29349 · Cited by 14
“6,49 Consistent with these studies, our research observed significant infiltration of various immune cells, including B cells, T cells, dendritic cells, neutrophils, and macrophages, into the lungs at 3 dpi.”
Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells
Kwon, D.-I., Park, S., Jeong, Y. L., Kim, Y., Min, J., Lee, C., Choi, J.-A., Choi, Y. H., Kong, H.-J., Choi, Y., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101362 · Cited by 12
Next-generation nanovaccine induces durable immunity and protects against SARS-CoV-2
Ross, K. A., Kelly, S. M., Phadke, K. S., Peroutka‐Bigus, N., Fasina, O. O., Siddoway, A. C., Mallapragada, S. K., Wannemuehler, M. J., Bellaire, B. H., & Narasimhan, B. (2024) · Acta Biomaterialia · doi:10.1016/j.actbio.2024.05.048 · Cited by 11
Upregulation of inflammatory genes and pathways links obesity to severe COVID-19
Currey, J. M., Ellsworth, C. R., Khatun, M. S., Wang, C., Chen, Z., Liu, S., Midkiff, C. C., Xiao, M. T., Ren, M., Liu, F., et al. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167322 · Cited by 12

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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