SARS‐CoV‐2 Productively Infects Human Hepatocytes and Induces Cell Death
Chunkyu Ko, Cho‐chin Cheng, Daniele Mistretta, Shubhankar Ambike, Julia Sacherl, Stoyan Velkov, Bo‐hung Liao, Romina Bester, Merve Gültan, Olga Polezhaeva, Alexander Herrmann, Constanze A Jakwerth, Carsten B Schmidt‐weber, Joachim J Bugert, Roman Wölfel, Vincent Grass, Sandra Essbauer, Daniel Schnepf, Oliver T Keppler, Florian W R Vondran, Andreas Pichlmair, Carolin Mogler, Gregor Ebert, Ulrike Protzer
Journal of Medical Virology, doi:10.1002/jmv.70156
SARS-CoV-2 infection is accompanied by elevated liver enzymes, and patients with pre-existing liver conditions experience more severe disease. While it was known that SARS-CoV-2 infects human hepatocytes, our study determines the mechanism of infection, demonstrates viral replication and spread, and highlights direct hepatocyte damage. Viral replication was readily detectable upon infection of primary human hepatocytes and hepatoma cells with the ancestral SARS-CoV-2, Delta, and Omicron variants. Hepatocytes express the SARS-CoV-2 receptor ACE2 and the host cell protease TMPRSS2, and knocking down ACE2 and TMPRSS2 impaired SARS-CoV-2 infection. Progeny viruses released from infected hepatocytes showed the typical coronavirus morphology by electron microscopy and proved infectious when transferred to fresh cells, indicating that hepatocytes can contribute to virus spread. Importantly, SARS-CoV-2 infection rapidly induced hepatocyte death in a replication-dependent fashion, with the Omicron variant showing faster onset but less extensive cell death. C57BL/6 wild-type mice infected with a mouse-adapted SARS-CoV-2 strain showed high levels of viral RNA in liver and lung tissues. ALT peaked when viral RNA was cleared from the liver. Liver histology revealed profound tissue damage and immune cell infiltration,
Author Contributions C.K., U.P. designed the study. C.K., C.C., G.E. and U.P. wrote the manuscript. C.K., C.C., D.M., S.A., J.S., B.L., R.B., O.P., M.G., C.A.J., J.J.B., R.W., V.G., S.E., C.M., G.E. performed experiments and analyzed the data. S.V. performed large data analysis. A.H., C.S.W., D.S., O.T.K., F.W.R.V., A.P., G.E. contributed essential material and instrumentation. All authors reviewed and agreed to the final version of the manuscript.
Ethics Statement The experimental procedures involving mice were conducted strictly according to the German regulations of the Society for Laboratory Animal Science (GV-SOLAS) and the European Health Law of the Federation of Laboratory Animal Science Associations (FELASA). Experiments were approved by the District Government of Upper Bavaria (ROB-55.2-2532. Vet_02-21-169).
Conflicts of Interest UP received grants from SCG Cell Therapy, and VirBio and personal fees from Abbott, Abbvie, Arbutus, Gilead, GSK, Leukocare, J&J, Roche, MSD, Sanofi, Sobi and Vaccitech. UP is a cofounder and shareholder of SCG Cell Therapy. The other authors declare no conflicts of interest. CAJ reports research funding from the German Center for Lung Research and an issued patent "Bradykinin B2 receptor antagonist for treatment of SARS-CoV2-infection" (EP3909646A1).
Supporting Information Additional supporting information can be found online in the Supporting Information section.
References
Abe, Hasegawa, Suzuki, Simultaneous Occurrence of Autoimmune Hepatitis and Autoimmune Hemolytic Anemia After COVID-19 Infection: Case Report and Literature Review, Clinical Journal of Gastroenterology
Afar, Vivanco, Hubert, Catalytic Cleavage of the Androgen-Regulated TMPRSS2 Protease Results in Its Secretion By Prostate and Prostate Cancer Epithelia, Cancer Research
Alluwaimi, Alshubaith, Al-Ali, Abohelaika, The Coronaviruses of Animals and Birds: Their Zoonosis, Vaccines, and Models for SARS-CoV and SARS-CoV2, Frontiers in Veterinary Science
Barreto, Cruz, Veras, COVID-19-Related Hyperglycemia Is Associated With Infection of Hepatocytes and Stimulation of Gluconeogenesis, Proceedings of the National Academy of Sciences
Beer, Crotta, Breithaupt, Impaired Immune Response Drives Age-Dependent Severity of Covid-19, Journal of Experimental Medicine
Chai, Hu, Zhang, Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection, bioRxiv
Chu, -W. Chan, -T. Yuen, Comparative Tropism, Replication Kinetics, and Cell Damage Profiling of SARS-CoV-2 and Sars-Cov With Implications for Clinical Manifestations, Transmissibility, and Laboratory Studies of COVID-19: an Observational Study, Lancet Microbe
Ding, Li, Chen, Association of Liver Abnormalities With In-Hospital Mortality in Patients With Covid-19, Journal of Hepatology
Finkel, Mizrahi, Nachshon, The Coding Capacity of SARS-CoV-2, Nature
Fraser, Beldar, Seitova, Structure and Activity of Human TMPRSS2 Protease Implicated in SARS-CoV-2 Activation, Nature Chemical Biology
Gordon, Mouncey, Al-Beidh, Interleukin-6 Receptor Antagonists in Critically Ill Patients With Covid-19, New England Journal of Medicine
Gordon, Tchesnokov, Woolner, Remdesivir Is a Direct-Acting Antiviral That Inhibits Rna-Dependent Rna Polymerase From Severe Acute Respiratory Syndrome Coronavirus 2 With High Potency, Journal of Biological Chemistry
Griffin, Levina, Lay, Vanadium(V) tris-3,5-di-tertbutylcatecholato Complex: Links Between Speciation and Anti-Proliferative Activity in Human Pancreatic Cancer Cells, Journal of Inorganic Biochemistry
Hamming, Timens, Bulthuis, Lely, Navis et al., Tissue Distribution of ACE2 Protein, the Functional Receptor for SARS Coronavirus. A First Step in Understanding SARS Pathogenesis, Journal of Pathology
Heinen, Khanal, Westhoven, Productive Infection of Primary Human Hepatocytes With SARS-CoV-2 Induces Antiviral and Proinflammatory Responses, Gut
Hikmet, Méar, Edvinsson, Micke, Uhlén et al., The Protein Expression Profile of ACE2 in Human Tissues, Molecular Systems Biology
Hoffmann, Kleine-Weber, Schroeder, SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell
Hogan, Stevens, Sahoo, High Frequency of SARS-CoV-2 Rnaemia and Association With Severe Disease, Clinical Infectious Diseases,
doi:10.1093/cid/ciaa1054Hui, Ho, Cheung, SARS-CoV-2 Omicron Variant Replication in Human Bronchus and Lung Ex Vivo, Nature
Jakwerth, Feuerherd, Guerth, Early Reduction of SARS-CoV-2-replication in Bronchial Epithelium By Kinin B(2) Receptor Antagonism, Journal of Molecular Medicine
Jones, Hunter, Is IL-6 a Key Cytokine Target for Therapy in COVID-19?, Nature Reviews Immunology
Kim, Lee, Yang, Kim, Kim et al., The Architecture of SARS-CoV-2 Transcriptome, Cell
Kleine, Riemer, Krech, Explanted Diseased Liversa Possible Source of Metabolic Competent Primary Human Hepatocytes, PLoS One
Ko, Chakraborty, Chou, Hepatitis B Virus Genome Recycling and De Novo Secondary Infection Events Maintain Stable Cccdna Levels, Journal of Hepatology
Li, Cui, Lin, Kupffer-Cell-Derived IL-6 Is Repurposed for Hepatocyte Dedifferentiation via Activating Progenitor Genes From Injury-Specific Enhancers, Cell Stem Cell
Li, Moore, Vasilieva, Angiotensin-Converting Enzyme 2 Is a Functional Receptor for the Sars Coronavirus, Nature
Liu, Zhang, Yang, The Role of interleukin-6 in Monitoring Severe Case of Coronavirus Disease 2019, EMBO Molecular Medicine
Mahlakõiv, Ritz, Mordstein, Combined Action of Type I and Type III Interferon Restricts Initial Replication of Severe Acute Respiratory Syndrome Coronavirus in the Lung but Fails to Inhibit Systemic Virus Spread, Journal of General Virology
Marjot, Eberhardt, Boettler, Impact of COVID-19 on the Liver and on the Care of Patients With Chronic Liver Disease, Hepatobiliary Cancer, and Liver Transplantation: An Updated EASL Position Paper, Journal of Hepatology
Marjot, Moon, Cook, Outcomes Following SARS-CoV-2 Infection in Patients With Chronic Liver Disease: An International Registry Study, Journal of Hepatology
Marjot, Webb, Barritt, COVID-19 and Liver Disease: Mechanistic and Clinical Perspectives, Nature Reviews Gastroenterology & Hepatology
Matsuyama, Nao, Shirato, Enhanced Isolation of SARS-CoV-2 By TMPRSS2-Expressing Cells, Proceedings of the National Academy of Sciences
Peacock, Goldhill, Zhou, The Furin Cleavage Site in the SARS-CoV-2 Spike Protein Is Required for Transmission in Ferrets, Nature Microbiology
Protzer, Maini, Knolle, Living in the Liver: Hepatic Infections, Nature Reviews Immunology
Puelles, Lütgehetmann, Lindenmeyer, Multiorgan and Renal Tropism of SARS-CoV-2, New England Journal of Medicine
Smet, Verhulst, Van Grunsven, Single Cell RNA Sequencing Analysis Did Not Predict Hepatocyte Infection by SARS-COV-2, Journal of Hepatology
Smirnova, Ivanova, Fedyakina, SARS-CoV-2 Establishes a Productive Infection in Hepatoma and Glioblastoma Multiforme Cell Lines, Cancers
Song, Hu, Yu, Little to No Expression of Angiotensin-Converting enzyme-2 on Most Human Peripheral Blood Immune Cells but Highly Expressed on Tissue Macrophages, Cytometry A,
doi:10.1002/cyto.a.24285Sonzogni, Previtali, Seghezzi, Liver Histopathology in Severe COVID 19 Respiratory Failure is Suggestive of Vascular Alterations, Liver International
Steiner, Kratzel, Barut, SARS-CoV-2 Biology and Host Interactions, Nature Reviews Microbiology
Talwani, Gilliam, Howell, Infectious Diseases and the Liver, Clinics in Liver Disease
Tan, Lim, Hong, Regulation of Cell Death During Infection By the Severe Acute Respiratory Syndrome Coronavirus and Other Coronaviruses, Cellular Microbiology
Wang, Liu, Liu, SARS-CoV-2 Infection of the Liver Directly Contributes to Hepatic Impairment in Patients With Covid-19, Journal of Hepatology
Wanner, Andrieux, Badia-I-Mompel, Molecular Consequences of SARS-CoV-2 Liver Tropism, Nature Metabolism
Weiss, Navas-Martin, Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus, Microbiology and Molecular Biology Reviews
Xu, Liu, Lu, Yang, Zheng, Liver Injury During Highly Pathogenic Human Coronavirus Infections, Liver International
Yan, Zhang, Ge, Architecture of a SARS-CoV-2 Mini Replication and Transcription Complex, Nature Communications
Yang, Han, Nilsson-Payant, A Human Pluripotent Stem Cell-Based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids, Cell Stem Cell
Yang, Zheng, Zhu, Asialoglycoprotein Receptor 1 Promotes SARS-CoV-2 Infection of Human Normal Hepatocytes, Signal Transduction and Targeted Therapy
Yuan, Ma, Xie, The Role of Cell Death in SARS-CoV-2 Infection, Signal Transduction and Targeted Therapy
Zhao, Ni, Gao, Recapitulation of SARS-CoV-2 Infection and Cholangiocyte Damage With Human Liver Ductal Organoids, Protein & Cell
Zheng, Li, Guo, Virulence and Pathogenesis of SARS-CoV-2 Infection in Rhesus Macaques: A Nonhuman Primate Model of COVID-19 Progression, PLoS Pathogens
Zhou, Yang, Wang, A Pneumonia Outbreak Associated With a New Coronavirus of Probable Bat Origin, Nature
Zhu, Zhang, Wang, A Novel Coronavirus From Patients With Pneumonia in China, 2019, New England Journal of Medicine
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