About: The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus

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About: The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus
Creator	Baric, Ralph Gralinski, Lisa Schäfer, Alexandra Josset, Laurence Li, Chengjun Neumann, Gabriele Fan, Shufang Mitchell, Hugh Bankhead Iii, Armand Eisfeld, Amie Katze, Michael Mcweeney, Shannon Waters, Katrina Mcdermott, Jason Tilton, Susan
topic	covid:a137eb51461b4a4ed3980aa5b9cb2f2c1cf0292a#this
Source	Medline; PMC
abstract	BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-016-0336-6) contains supplementary material, which is available to authorized users.
has issue date	2016-09-23(xsd:dateTime)
bibo:doi	10.1186/s12918-016-0336-6
bibo:pmid	27663205
has license	cc-by
sha1sum (hex)	a137eb51461b4a4ed3980aa5b9cb2f2c1cf0292a
schema:url	https://doi.org/10.1186/s12918-016-0336-6
resource representing a document's title	The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus
has PubMed Central identifier	PMC5035469
has PubMed identifier	27663205
schema:publication	BMC Syst Biol
resource representing a document's body	covid:a137eb51461b4a4ed3980aa5b9cb2f2c1cf0292a#body_text
is http://vocab.deri.ie/void#inDataset of	https://covidontheweb.inria.fr:4443/about/id/http/ns.inria.fr/covid19/a137eb51461b4a4ed3980aa5b9cb2f2c1cf0292a
is schema:about of	named entity 'model' named entity 'excessive' named entity 'inhibition' named entity 'PATHOGENESIS' named entity 'EXCESSIVE' named entity 'VIRAL REPLICATION' named entity 'TARGETS' named entity 'PATHOGENIC' named entity 'REPLICATION' named entity 'VIRUS' named entity 'DICHOTOMY' named entity 'THEIR' named entity 'REGULATORY' named entity 'VIRUSES' named entity 'EMPLOY' named entity 'MODEL' named entity 'HIGHLY' named entity 'TRANSCRIPTIONAL NETWORK' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS' named entity 'UNDERSTOOD' named entity 'INHIBITION' named entity 'CAUSE' named entity 'IMMUNE RESPONSE' named entity 'HOST IMMUNE RESPONSE' named entity 'USED' named entity 'IMMUNE' named entity 'RATHER' named entity 'MICE' named entity 'COMPLEX' named entity 'SIGNALING' named entity 'PP1' named entity 'EFFECT' named entity 'TO INVESTIGATE' named entity 'MODEL OF' named entity 'BACKGROUND' named entity 'POORLY' named entity 'EXACERBATES' named entity 'NETWORK MODEL' named entity 'TNF' named entity 'SARS CORONAVIRUS' named entity 'INFECTION' named entity 'SARS-COV INFECTION' named entity 'INFECTIONS' named entity 'STRATEGIES' named entity 'PATHOGENICITY' named entity 'INVESTIGATION' named entity 'CANDIDATE' named entity 'KNOWN' covid:arg/a137eb51461b4a4ed3980aa5b9cb2f2c1cf0292a named entity 'reduces' named entity 'dichotomy' named entity 'remains' named entity 'SARS-CoV' named entity 'highly' named entity 'infection' named entity 'TNFα' named entity 'pathogenic virus' named entity 'mice' named entity 'viruses' named entity 'SARS coronavirus' named entity 'Tnfrsf1a' named entity 'gene' named entity 'mice' named entity 'mice' named entity 'pathogenesis'

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