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Article: SARS-CoV-2 induces a more robust innate immune response and replicates less efficiently than SARS-CoV in the human intestines: An ex vivo study with implications on pathogenesis of COVID-19

TitleSARS-CoV-2 induces a more robust innate immune response and replicates less efficiently than SARS-CoV in the human intestines: An ex vivo study with implications on pathogenesis of COVID-19
Authors
KeywordsCOVID-19
Immune Activation
Intestine
Replication
SARS-CoV
Issue Date2021
PublisherElsevier: Open Access Journals. The Journal's web site is located at https://www.cmghjournal.org/
Citation
Cellular and Molecular Gastroenterology and Hepatology, 2021, v. 11 n. 3, p. 771-781 How to Cite?
AbstractBackground and Aims: Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile. Methods: Human intestinal tissues were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines. Results: SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues. Conclusion: Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human gut and suggested that the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for COVID-19 and SARS, which might be the result of a more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine.
Persistent Identifierhttp://hdl.handle.net/10722/298771
ISSN
2021 Impact Factor: 8.797
2020 SCImago Journal Rankings: 3.417
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChu, H-
dc.contributor.authorChan, JFW-
dc.contributor.authorWang, Y-
dc.contributor.authorYuen, TTT-
dc.contributor.authorChai, Y-
dc.contributor.authorShuai, H-
dc.contributor.authorYANG, D-
dc.contributor.authorHu, B-
dc.contributor.authorHuang, X-
dc.contributor.authorZhang, X-
dc.contributor.authorHou, Y-
dc.contributor.authorCai, JP-
dc.contributor.authorZhang, J-
dc.contributor.authorZhou, J-
dc.contributor.authorYuan, S-
dc.contributor.authorTo, KKW-
dc.contributor.authorHung, IFN-
dc.contributor.authorCheung, TT-
dc.contributor.authorNg, ATL-
dc.contributor.authorChan, HYI-
dc.contributor.authorWong, IYH-
dc.contributor.authorLaw, SYK-
dc.contributor.authorFoo, DCC-
dc.contributor.authorLeung, WK-
dc.contributor.authorYuen, KY-
dc.date.accessioned2021-04-12T03:03:08Z-
dc.date.available2021-04-12T03:03:08Z-
dc.date.issued2021-
dc.identifier.citationCellular and Molecular Gastroenterology and Hepatology, 2021, v. 11 n. 3, p. 771-781-
dc.identifier.issn2352-345X-
dc.identifier.urihttp://hdl.handle.net/10722/298771-
dc.description.abstractBackground and Aims: Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile. Methods: Human intestinal tissues were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines. Results: SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues. Conclusion: Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human gut and suggested that the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for COVID-19 and SARS, which might be the result of a more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine.-
dc.languageeng-
dc.publisherElsevier: Open Access Journals. The Journal's web site is located at https://www.cmghjournal.org/-
dc.relation.ispartofCellular and Molecular Gastroenterology and Hepatology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCOVID-19-
dc.subjectImmune Activation-
dc.subjectIntestine-
dc.subjectReplication-
dc.subjectSARS-CoV-
dc.titleSARS-CoV-2 induces a more robust innate immune response and replicates less efficiently than SARS-CoV in the human intestines: An ex vivo study with implications on pathogenesis of COVID-19-
dc.typeArticle-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailShuai, H: shuaihp@connect.hku.hk-
dc.identifier.emailHu, B: bingjie@hku.hk-
dc.identifier.emailCai, JP: caijuice@hku.hk-
dc.identifier.emailZhang, J: zhangajx@hkucc.hku.hk-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hku.hk-
dc.identifier.emailHung, IFN: ivanhung@hkucc.hku.hk-
dc.identifier.emailCheung, TT: cheung68@hku.hk-
dc.identifier.emailNg, ATL: ada5022@hku.hk-
dc.identifier.emailChan, HYI: ivyhchan@hku.hk-
dc.identifier.emailWong, IYH: iyhwong@hku.hk-
dc.identifier.emailLaw, SYK: slaw@hku.hk-
dc.identifier.emailFoo, DCC: ccfoo@hku.hk-
dc.identifier.emailLeung, WK: waikleung@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityZhang, J=rp00413-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityYuan, S=rp02640-
dc.identifier.authorityTo, KKW=rp01384-
dc.identifier.authorityHung, IFN=rp00508-
dc.identifier.authorityCheung, TT=rp02129-
dc.identifier.authorityWong, IYH=rp02293-
dc.identifier.authorityLaw, SYK=rp00437-
dc.identifier.authorityFoo, DCC=rp01899-
dc.identifier.authorityLeung, WK=rp01479-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.jcmgh.2020.09.017-
dc.identifier.pmid33010495-
dc.identifier.pmcidPMC7527315-
dc.identifier.scopuseid_2-s2.0-85100051853-
dc.identifier.hkuros322084-
dc.identifier.volume11-
dc.identifier.issue3-
dc.identifier.spage771-
dc.identifier.epage781-
dc.identifier.isiWOS:000621254400007-
dc.publisher.placeUnited States-

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