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Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells.
Cell Rep. 2020 07 07; 32(1):107863.CR

Abstract

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is an unprecedented worldwide health problem that requires concerted and global approaches to stop the coronavirus 2019 (COVID-19) pandemic. Although SARS-CoV-2 primarily targets lung epithelium cells, there is growing evidence that the intestinal epithelium is also infected. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of the SARS-CoV-2 life cycle in human intestinal epithelial cells (hIECs). Our results demonstrate that hIECs fully support SARS-CoV-2 infection, replication, and production of infectious de novo virus particles. We found that viral infection elicits an extremely robust intrinsic immune response where interferon-mediated responses are efficient at controlling SARS-CoV-2 replication and de novo virus production. Taken together, our data demonstrate that hIECs are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing to increasing patient viremia and fueling an exacerbated cytokine response.

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Authors+Show Affiliations

Stanifer ML
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg 69120, Germany; Research Group "Cellular polarity and viral infection," German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. Electronic address: m.stanifer@dkfz.de.
Kee C
Research Group "Cellular polarity and viral infection," German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg 69120, Germany.
Cortese M
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg 69120, Germany.
Zumaran CM
Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg 69120, Germany.
Triana S
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany; Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg 69120, Germany.
Mukenhirn M
Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg 69120, Germany.
Kraeusslich HG
Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg 69120, Germany.
Alexandrov T
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Bartenschlager R
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg 69120, Germany; Division "Virus-associated Carcinogenesis," German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; German Center for Infection Research, Heidelberg Partner site, Heidelberg 69120, Germany.
Boulant S
Research Group "Cellular polarity and viral infection," German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg 69120, Germany. Electronic address: s.boulant@dkfz.de.

MeSH

BetacoronavirusCOVID-19Caco-2 CellsCell Line, TumorColonCoronavirus InfectionsCytokine Release SyndromeCytokinesEpithelial CellsHumansInterferonsIntestinal MucosaPandemicsPneumonia, ViralSARS-CoV-2Severe Acute Respiratory SyndromeVirus ReplicationInterferon Lambda

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32610043

Citation

Stanifer, Megan L., et al. "Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells." Cell Reports, vol. 32, no. 1, 2020, p. 107863.
Stanifer ML, Kee C, Cortese M, et al. Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells. Cell Rep. 2020;32(1):107863.
Stanifer, M. L., Kee, C., Cortese, M., Zumaran, C. M., Triana, S., Mukenhirn, M., Kraeusslich, H. G., Alexandrov, T., Bartenschlager, R., & Boulant, S. (2020). Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells. Cell Reports, 32(1), 107863. https://doi.org/10.1016/j.celrep.2020.107863
Stanifer ML, et al. Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells. Cell Rep. 2020 07 7;32(1):107863. PubMed PMID: 32610043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells. AU - Stanifer,Megan L, AU - Kee,Carmon, AU - Cortese,Mirko, AU - Zumaran,Camila Metz, AU - Triana,Sergio, AU - Mukenhirn,Markus, AU - Kraeusslich,Hans-Georg, AU - Alexandrov,Theodore, AU - Bartenschlager,Ralf, AU - Boulant,Steeve, Y1 - 2020/06/19/ PY - 2020/04/22/received PY - 2020/05/18/revised PY - 2020/06/15/accepted PY - 2020/7/2/pubmed PY - 2020/7/21/medline PY - 2020/7/2/entrez KW - IFN KW - ISGs KW - SARS-CoV-2 KW - human intestinal epithelial cells KW - interferon KW - interferon lambda KW - interferon stimulted genes KW - intrinsic immunity KW - organoids SP - 107863 EP - 107863 JF - Cell reports JO - Cell Rep VL - 32 IS - 1 N2 - Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is an unprecedented worldwide health problem that requires concerted and global approaches to stop the coronavirus 2019 (COVID-19) pandemic. Although SARS-CoV-2 primarily targets lung epithelium cells, there is growing evidence that the intestinal epithelium is also infected. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of the SARS-CoV-2 life cycle in human intestinal epithelial cells (hIECs). Our results demonstrate that hIECs fully support SARS-CoV-2 infection, replication, and production of infectious de novo virus particles. We found that viral infection elicits an extremely robust intrinsic immune response where interferon-mediated responses are efficient at controlling SARS-CoV-2 replication and de novo virus production. Taken together, our data demonstrate that hIECs are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing to increasing patient viremia and fueling an exacerbated cytokine response. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/32610043/Critical_Role_of_Type_III_Interferon_in_Controlling_SARS_CoV_2_Infection_in_Human_Intestinal_Epithelial_Cells_ DB - PRIME DP - Unbound Medicine ER -