SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death

Yue, Yuan; Nabar, Neel R.; Shi, Chong-Shan; Kamenyeva, Olena; Xiao, Xincai; Hwang, Il‐Young; Wang, Min; Kehrl, John H.

doi:10.1038/s41419-018-0917-y

Cited by 209 publications

(211 citation statements)

References 55 publications

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“…MERS-CoV infection activates both intrinsic and extrinsic pathways of apoptosis, exacerbating viral pathogenesis [21]. Other than apoptosis, SARS-CoV induces RIP3-mediated necrosis through induction of ORF3a oligomerization [80]. Generally, highly pathogenic HCoVs are capable of activating different cell death programmes more efficiently.…”

Section: To Kill or Not To Kill?mentioning

confidence: 99%

A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses

Fung

Yuen

et al. 2020

Emerging Microbes & Infections

354

370

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World Health Organization has declared the ongoing outbreak of coronavirus disease 2019 a Public Health Emergency of International Concern. The virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. Human infection with SARS-CoV-2 leads to a wide range of clinical manifestations ranging from asymptomatic, mild, moderate to severe. The severe cases present with pneumonia, which can progress to acute respiratory distress syndrome. The outbreak provides an opportunity for real-time tracking of an animal coronavirus that has just crossed species barrier to infect humans. The outcome of SARS-CoV-2 infection is largely determined by virus-host interaction. Here, we review the discovery, zoonotic origin, animal hosts, transmissibility and pathogenicity of SARS-CoV-2 in relation to its interplay with host antiviral defense. A comparison with SARS-CoV, Middle East respiratory syndrome coronavirus, community-acquired human coronaviruses and other pathogenic viruses including human immunodeficiency viruses is made. We summarize current understanding of the induction of a proinflammatory cytokine storm by other highly pathogenic human coronaviruses, their adaptation to humans and their usurpation of the cell death programmes. Important questions concerning the interaction between SARS-CoV-2 and host antiviral defence, including asymptomatic and presymptomatic virus shedding, are also discussed. ARTICLE HISTORY

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Section: To Kill or Not To Kill?mentioning

confidence: 99%

A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses

Fung

Yuen

et al. 2020

Emerging Microbes & Infections

354

370

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“…While some genes were shared between the tissue and cell programs (e.g., many virus-related genes, such as CEACAM5, CXCL17, SLPI, and HLA-DRA), the cell programs further captured unique biological functions and activities. For example, dual positive lung secretory cells differentially expressed genes involved in TNF signaling including RIPK3, a key regulator of inflammatory cell death via necroptosis, previously implicated in SARS-CoV pathogenesis 84 . Both lung dual positive secretory and multiciliated cells differentially expressed lysosomal genes (MFSD8, CTSS, CTNS, CTSH), potentially relevant for endolysosomal entry of coronaviruses 85 .…”

Section: An Immune Gene Program Associated With Ace2 + Tmprss2 + Exprmentioning

confidence: 99%

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

Muus

Luecken

Eraslan

et al. 2020

Preprint

250

326

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The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2 + TMPRSS2 + cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis.

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“…Viral replication within the lungs in conjunction with an increased influx of innate immune cells mediates tissue damage and may fuel an auto-amplification inflammatory loop, potentially driven by NFκB, and ultimately leading to ARDS and respiratory failure. Interestingly, virulent human coronaviruses have been shown to promote multiple form of necrotic cell death such as RIPK3-dependent necroptosis and caspase-1-dependent pyroptosis 35 . These pathways have also been implicated in influenza-induced ARDS in mice and humans 36,37 .…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients

Hadjadj

Yatim

Barnabei

et al. 2020

Preprint

268

312

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SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death

Cited by 209 publications

References 55 publications

A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses

A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients

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