Infection of bat and human intestinal organoids by SARS-CoV-2
A novel coronavirus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally 1 , 2 . As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on ful...
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| Veröffentlicht in: | Nature medicine 2020-07, Vol.26 (7), p.1077-1083 |
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| creator | Zhou, Jie Li, Cun Liu, Xiaojuan Chiu, Man Chun Zhao, Xiaoyu Wang, Dong Wei, Yuxuan Lee, Andrew Zhang, Anna Jinxia Chu, Hin Cai, Jian-Piao Yip, Cyril Chik-Yan Chan, Ivy Hau-Yee Wong, Kenneth Kak-Yuen Tsang, Owen Tak-Yin Chan, Kwok-Hung Chan, Jasper Fuk-Woo To, Kelvin Kai-Wang Chen, Honglin Yuen, Kwok Yung |
| description | A novel coronavirus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally
1
,
2
. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats
1
,
2
. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the
Rhinolophus sinicus
species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection
3
,
4
. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.
Bat and human intestinal organoids can support replication of SARS-CoV-2, enabling further characterization of the virus lifecycle and investigation of potential mechanisms of enteric infection in COVID-19. |
| doi_str_mv | 10.1038/s41591-020-0912-6 |
| format | Article |
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1
,
2
. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats
1
,
2
. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the
Rhinolophus sinicus
species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection
3
,
4
. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.
Bat and human intestinal organoids can support replication of SARS-CoV-2, enabling further characterization of the virus lifecycle and investigation of potential mechanisms of enteric infection in COVID-19.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/s41591-020-0912-6</identifier><identifier>PMID: 32405028</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/326/596/2078 ; 631/326/596/2557 ; Animals ; Bats ; Betacoronavirus - pathogenicity ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cell culture ; Cell Differentiation ; Cells, Cultured ; Child, Preschool ; Chiroptera - virology ; Chlorocebus aethiops ; Coronaviridae ; Coronavirus Infections - pathology ; Coronavirus Infections - transmission ; Coronavirus Infections - virology ; Coronaviruses ; COVID-19 ; Diarrhea ; Disease transmission ; Enterocytes - pathology ; Enterocytes - physiology ; Enterocytes - virology ; Epithelium ; Female ; Gastrointestinal symptoms ; Genomes ; Health aspects ; Homology ; Humans ; Infant ; Infections ; Infectious Diseases ; Intestinal Mucosa - pathology ; Intestinal Mucosa - virology ; Intestine ; Intestines ; Intestines - pathology ; Intestines - virology ; Letter ; Male ; Metabolic Diseases ; Methods ; Molecular Medicine ; Neurosciences ; Nucleotide sequence ; Organoids ; Organoids - pathology ; Organoids - virology ; Pandemics ; Physiological aspects ; Pneumonia, Viral - pathology ; Pneumonia, Viral - transmission ; Pneumonia, Viral - virology ; Replication ; Respiratory diseases ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; Robustness ; SARS-CoV-2 ; Sequence analysis ; Severe acute respiratory syndrome coronavirus 2 ; Vero Cells ; Viral diseases ; Viral Load - genetics ; Viral Load - methods ; Viral Tropism - physiology ; Viruses</subject><ispartof>Nature medicine, 2020-07, Vol.26 (7), p.1077-1083</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2020</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c637t-d6eb49388dcccb45ded91f4be2166434c62868be0d673b870ef9eb68d67df8fd3</cites><orcidid>0000-0002-2948-3873 ; 0000-0002-8432-3282 ; 0000-0001-9503-6396 ; 0000-0001-5108-8338 ; 0000-0003-1771-8249 ; 0000-0001-7371-503X ; 0000-0002-0347-9104 ; 0000-0002-2083-1552</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41591-020-0912-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41591-020-0912-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32405028$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Jie</creatorcontrib><creatorcontrib>Li, Cun</creatorcontrib><creatorcontrib>Liu, Xiaojuan</creatorcontrib><creatorcontrib>Chiu, Man Chun</creatorcontrib><creatorcontrib>Zhao, Xiaoyu</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Wei, Yuxuan</creatorcontrib><creatorcontrib>Lee, Andrew</creatorcontrib><creatorcontrib>Zhang, Anna Jinxia</creatorcontrib><creatorcontrib>Chu, Hin</creatorcontrib><creatorcontrib>Cai, Jian-Piao</creatorcontrib><creatorcontrib>Yip, Cyril Chik-Yan</creatorcontrib><creatorcontrib>Chan, Ivy Hau-Yee</creatorcontrib><creatorcontrib>Wong, Kenneth Kak-Yuen</creatorcontrib><creatorcontrib>Tsang, Owen Tak-Yin</creatorcontrib><creatorcontrib>Chan, Kwok-Hung</creatorcontrib><creatorcontrib>Chan, Jasper Fuk-Woo</creatorcontrib><creatorcontrib>To, Kelvin Kai-Wang</creatorcontrib><creatorcontrib>Chen, Honglin</creatorcontrib><creatorcontrib>Yuen, Kwok Yung</creatorcontrib><title>Infection of bat and human intestinal organoids by SARS-CoV-2</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>A novel coronavirus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally
1
,
2
. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats
1
,
2
. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the
Rhinolophus sinicus
species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection
3
,
4
. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.
Bat and human intestinal organoids can support replication of SARS-CoV-2, enabling further characterization of the virus lifecycle and investigation of potential mechanisms of enteric infection in COVID-19.</description><subject>631/326/596/2078</subject><subject>631/326/596/2557</subject><subject>Animals</subject><subject>Bats</subject><subject>Betacoronavirus - pathogenicity</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cell culture</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Child, Preschool</subject><subject>Chiroptera - virology</subject><subject>Chlorocebus aethiops</subject><subject>Coronaviridae</subject><subject>Coronavirus Infections - pathology</subject><subject>Coronavirus Infections - transmission</subject><subject>Coronavirus Infections - virology</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Diarrhea</subject><subject>Disease transmission</subject><subject>Enterocytes - pathology</subject><subject>Enterocytes - physiology</subject><subject>Enterocytes - virology</subject><subject>Epithelium</subject><subject>Female</subject><subject>Gastrointestinal symptoms</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Homology</subject><subject>Humans</subject><subject>Infant</subject><subject>Infections</subject><subject>Infectious Diseases</subject><subject>Intestinal Mucosa - pathology</subject><subject>Intestinal Mucosa - virology</subject><subject>Intestine</subject><subject>Intestines</subject><subject>Intestines - pathology</subject><subject>Intestines - virology</subject><subject>Letter</subject><subject>Male</subject><subject>Metabolic Diseases</subject><subject>Methods</subject><subject>Molecular Medicine</subject><subject>Neurosciences</subject><subject>Nucleotide sequence</subject><subject>Organoids</subject><subject>Organoids - pathology</subject><subject>Organoids - virology</subject><subject>Pandemics</subject><subject>Physiological aspects</subject><subject>Pneumonia, Viral - 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genetics</topic><topic>Viral Load - methods</topic><topic>Viral Tropism - physiology</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Jie</creatorcontrib><creatorcontrib>Li, Cun</creatorcontrib><creatorcontrib>Liu, Xiaojuan</creatorcontrib><creatorcontrib>Chiu, Man Chun</creatorcontrib><creatorcontrib>Zhao, Xiaoyu</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Wei, Yuxuan</creatorcontrib><creatorcontrib>Lee, Andrew</creatorcontrib><creatorcontrib>Zhang, Anna Jinxia</creatorcontrib><creatorcontrib>Chu, Hin</creatorcontrib><creatorcontrib>Cai, Jian-Piao</creatorcontrib><creatorcontrib>Yip, Cyril Chik-Yan</creatorcontrib><creatorcontrib>Chan, Ivy Hau-Yee</creatorcontrib><creatorcontrib>Wong, Kenneth Kak-Yuen</creatorcontrib><creatorcontrib>Tsang, Owen Tak-Yin</creatorcontrib><creatorcontrib>Chan, Kwok-Hung</creatorcontrib><creatorcontrib>Chan, Jasper Fuk-Woo</creatorcontrib><creatorcontrib>To, Kelvin Kai-Wang</creatorcontrib><creatorcontrib>Chen, Honglin</creatorcontrib><creatorcontrib>Yuen, Kwok Yung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Jie</au><au>Li, Cun</au><au>Liu, Xiaojuan</au><au>Chiu, Man Chun</au><au>Zhao, Xiaoyu</au><au>Wang, Dong</au><au>Wei, Yuxuan</au><au>Lee, Andrew</au><au>Zhang, Anna Jinxia</au><au>Chu, Hin</au><au>Cai, Jian-Piao</au><au>Yip, Cyril Chik-Yan</au><au>Chan, Ivy Hau-Yee</au><au>Wong, Kenneth Kak-Yuen</au><au>Tsang, Owen Tak-Yin</au><au>Chan, Kwok-Hung</au><au>Chan, Jasper Fuk-Woo</au><au>To, Kelvin Kai-Wang</au><au>Chen, Honglin</au><au>Yuen, Kwok Yung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Infection of bat and human intestinal organoids by SARS-CoV-2</atitle><jtitle>Nature medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>26</volume><issue>7</issue><spage>1077</spage><epage>1083</epage><pages>1077-1083</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><abstract>A novel coronavirus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally
1
,
2
. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats
1
,
2
. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the
Rhinolophus sinicus
species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection
3
,
4
. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.
Bat and human intestinal organoids can support replication of SARS-CoV-2, enabling further characterization of the virus lifecycle and investigation of potential mechanisms of enteric infection in COVID-19.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>32405028</pmid><doi>10.1038/s41591-020-0912-6</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-2948-3873</orcidid><orcidid>https://orcid.org/0000-0002-8432-3282</orcidid><orcidid>https://orcid.org/0000-0001-9503-6396</orcidid><orcidid>https://orcid.org/0000-0001-5108-8338</orcidid><orcidid>https://orcid.org/0000-0003-1771-8249</orcidid><orcidid>https://orcid.org/0000-0001-7371-503X</orcidid><orcidid>https://orcid.org/0000-0002-0347-9104</orcidid><orcidid>https://orcid.org/0000-0002-2083-1552</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-8956 |
| ispartof | Nature medicine, 2020-07, Vol.26 (7), p.1077-1083 |
| issn | 1078-8956 1546-170X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2403028815 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature |
| subjects | 631/326/596/2078 631/326/596/2557 Animals Bats Betacoronavirus - pathogenicity Biomedical and Life Sciences Biomedicine Cancer Research Cell culture Cell Differentiation Cells, Cultured Child, Preschool Chiroptera - virology Chlorocebus aethiops Coronaviridae Coronavirus Infections - pathology Coronavirus Infections - transmission Coronavirus Infections - virology Coronaviruses COVID-19 Diarrhea Disease transmission Enterocytes - pathology Enterocytes - physiology Enterocytes - virology Epithelium Female Gastrointestinal symptoms Genomes Health aspects Homology Humans Infant Infections Infectious Diseases Intestinal Mucosa - pathology Intestinal Mucosa - virology Intestine Intestines Intestines - pathology Intestines - virology Letter Male Metabolic Diseases Methods Molecular Medicine Neurosciences Nucleotide sequence Organoids Organoids - pathology Organoids - virology Pandemics Physiological aspects Pneumonia, Viral - pathology Pneumonia, Viral - transmission Pneumonia, Viral - virology Replication Respiratory diseases Reverse Transcriptase Polymerase Chain Reaction Ribonucleic acid RNA Robustness SARS-CoV-2 Sequence analysis Severe acute respiratory syndrome coronavirus 2 Vero Cells Viral diseases Viral Load - genetics Viral Load - methods Viral Tropism - physiology Viruses |
| title | Infection of bat and human intestinal organoids by SARS-CoV-2 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T00%3A53%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Infection%20of%20bat%20and%20human%20intestinal%20organoids%20by%20SARS-CoV-2&rft.jtitle=Nature%20medicine&rft.au=Zhou,%20Jie&rft.date=2020-07-01&rft.volume=26&rft.issue=7&rft.spage=1077&rft.epage=1083&rft.pages=1077-1083&rft.issn=1078-8956&rft.eissn=1546-170X&rft_id=info:doi/10.1038/s41591-020-0912-6&rft_dat=%3Cgale_proqu%3EA629420734%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2423337944&rft_id=info:pmid/32405028&rft_galeid=A629420734&rfr_iscdi=true |