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

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About: SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death
Creator	Wang, Min Shi, Chong-Shan Yue, Yuan Kamenyeva, Olena Hwang, Il-Young Xiao, Xun Kehrl, John Nabar, Neel
source	Medline; PMC
abstract	The molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames (SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways. We show that SARS 3a interacts with Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS 3a helping drive necrotic cell death. In addition, by inserting into lysosomal membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently, Transcription Factor EB (TFEB) translocates to the nucleus increasing the transcription of autophagy- and lysosome-related genes. Finally, SARS 3a activates caspase-1 either directly or via an enhanced potassium efflux, which triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation—all likely contributing to the clinical manifestations of SARS-CoV infection.
has issue date	2018-09-05(xsd:dateTime)
bibo:doi	10.1038/s41419-018-0917-y
bibo:pmid	30185776
has license	cc-by
sha1sum (hex)	263a93d919f1c783a014ddb3f1b15d7ad3a3553b
schema:url	https://doi.org/10.1038/s41419-018-0917-y
resource representing a document's title	SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death
has PubMed Central identifier	PMC6125346
has PubMed identifier	30185776
schema:publication	Cell Death Dis
resource representing a document's body	covid:263a93d919f1c783a014ddb3f1b15d7ad3a3553b#body_text
is schema:about of	named entity 'NECROTIC CELL DEATH' named entity 'PROTEIN 3' named entity 'SUMMARY' named entity 'INFECTIONS' named entity 'SARS' named entity 'UNDERSTOOD' named entity 'SARS-COV INFECTION' named entity 'MOLECULAR' named entity 'ITS' named entity 'MEMBRANES' named entity 'CASPASE-1' named entity 'CONTRIBUTING' named entity 'PROTEIN ' named entity 'TRIGGERS' named entity 'OPEN READING FRAMES' named entity 'LARGEST' named entity 'NECROTIC CELL DEATH' named entity 'DRIVES' named entity 'OPEN READING FRAME' named entity 'INSERTING' named entity 'POTASSIUM' named entity 'LATE' named entity 'GENES' named entity 'RIP3' named entity 'GOLGI' named entity 'CLINICAL MANIFESTATIONS' named entity 'INFLAMMATORY' named entity 'PATHOLOGY' named entity 'RANGE' named entity 'MECHANISMS' named entity 'DYSFUNCTION' named entity 'LIKELY' named entity 'RELATED' named entity 'ENHANCED' named entity 'TRANS' named entity 'LYSOSOMAL' named entity 'ACTIVATION' named entity 'DRIVE' named entity 'EITHER' named entity 'APOPTOTIC CELL DEATH PATHWAY' named entity 'RECEPTOR INTERACTING PROTEIN' named entity 'PATHWAYS' named entity 'SARS-COV' named entity 'NETWORK' named entity 'LUNG' named entity 'LYSOSOME' named entity 'PREVIOUSLY' named entity 'DAMAGE' named entity 'ACCESSORY PROTEIN' named entity 'EFFLUX' named entity 'EFFECTS' named entity 'TARGETS' named entity 'PATHOPHYSIOLOGIC' named entity 'NLRP3' named entity 'ADDITION' named entity 'TRANSCRIPTION' named entity 'CORONAVIRUS' named entity 'OCCURS DURING' named entity 'INFLAMMASOME' named entity 'CAUSES' named entity 'NUCLEUS' named entity 'NON-' named entity 'ACTIVATES' named entity 'SEVERE' named entity 'MEDIATED' named entity 'TRANSCRIPTION FACTOR EB' named entity 'DIRECTLY' named entity 'INCREASING' named entity 'EXAMINING' named entity 'SARS' named entity 'ASSEMBLY' named entity 'UNDERLYING' named entity 'HERE' named entity 'EXTEND'

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