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Article: Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity

TitleTargeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity
Authors
Issue Date2021
PublisherAmerican Association for the Advancement of Science: Science Advances. The Journal's web site is located at http://www.scienceadvances.org/
Citation
Science Advances, 2021, v. 7 n. 25, p. article no. eabf8577 How to Cite?
AbstractInfection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R–like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2– and SARS-CoV–induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2–inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.
Persistent Identifierhttp://hdl.handle.net/10722/304558
ISSN
2023 Impact Factor: 11.7
2023 SCImago Journal Rankings: 4.483
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChu, H-
dc.contributor.authorShuai, H-
dc.contributor.authorHou, Y-
dc.contributor.authorZhang, X-
dc.contributor.authorWen, L-
dc.contributor.authorHuang, X-
dc.contributor.authorHu, BJ-
dc.contributor.authorYang, D-
dc.contributor.authorWang, Y-
dc.contributor.authorYoon, C-
dc.contributor.authorWong, BHY-
dc.contributor.authorLi, C-
dc.contributor.authorZHAO, X-
dc.contributor.authorPoon, VKM-
dc.contributor.authorCai, JP-
dc.contributor.authorWong, KKY-
dc.contributor.authorYeung, ML-
dc.contributor.authorZhou, J-
dc.contributor.authorAu Yeung, RKH-
dc.contributor.authorYuan, S-
dc.contributor.authorJin, DY-
dc.contributor.authorKok, KH-
dc.contributor.authorPerlman, S-
dc.contributor.authorChan, JFW-
dc.contributor.authorYuen, KY-
dc.date.accessioned2021-09-23T09:01:46Z-
dc.date.available2021-09-23T09:01:46Z-
dc.date.issued2021-
dc.identifier.citationScience Advances, 2021, v. 7 n. 25, p. article no. eabf8577-
dc.identifier.issn2375-2548-
dc.identifier.urihttp://hdl.handle.net/10722/304558-
dc.description.abstractInfection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R–like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2– and SARS-CoV–induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2–inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.-
dc.languageeng-
dc.publisherAmerican Association for the Advancement of Science: Science Advances. The Journal's web site is located at http://www.scienceadvances.org/-
dc.relation.ispartofScience Advances-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleTargeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity-
dc.typeArticle-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailShuai, H: shuaihp@connect.hku.hk-
dc.identifier.emailZhang, X: zxzxzx@connect.hku.hk-
dc.identifier.emailYang, D: dongfang@hku.hk-
dc.identifier.emailYoon, C: chaemin@hku.hk-
dc.identifier.emailLi, C: licun@hku.hk-
dc.identifier.emailPoon, VKM: vinpoon@hku.hk-
dc.identifier.emailCai, JP: caijuice@hku.hk-
dc.identifier.emailWong, KKY: kkywong@hku.hk-
dc.identifier.emailYeung, ML: pmlyeung@hku.hk-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailAu Yeung, RKH: rex.auyeung@hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailJin, DY: dyjin@hku.hk-
dc.identifier.emailKok, KH: khkok@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityLi, C=rp02783-
dc.identifier.authorityWong, KKY=rp01392-
dc.identifier.authorityYeung, ML=rp01402-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityAu Yeung, RKH=rp01877-
dc.identifier.authorityYuan, S=rp02640-
dc.identifier.authorityJin, DY=rp00452-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1126/sciadv.abf8577-
dc.identifier.pmid34134991-
dc.identifier.pmcidPMC8208716-
dc.identifier.scopuseid_2-s2.0-85108024168-
dc.identifier.hkuros325602-
dc.identifier.volume7-
dc.identifier.issue25-
dc.identifier.spagearticle no. eabf8577-
dc.identifier.epagearticle no. eabf8577-
dc.identifier.isiWOS:000664958400027-
dc.publisher.placeUnited States-

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