About: Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na(+)/K(+) transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses

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About: Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na(+)/K(+) transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses 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	Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na(+)/K(+) transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses
Creator	Iwasaki, Masaharu Minder, Petra De La Torre, Juan Kuhn, Jens Torbett, Bruce Yates Iii, John Yíngyú N Caì,
Source	Medline; PMC
abstract	Several mammalian arenaviruses (mammarenaviruses) cause hemorrhagic fevers in humans and pose serious public health concerns in their endemic regions. Additionally, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. Concerns about human-pathogenic mammarenaviruses are exacerbated by of the lack of licensed vaccines, and current anti-mammarenavirus therapy is limited to off-label use of ribavirin that is only partially effective. Detailed understanding of virus/host-cell interactions may facilitate the development of novel anti-mammarenavirus strategies by targeting components of the host-cell machinery that are required for efficient virus multiplication. Here we document the generation of a recombinant LCMV encoding a nucleoprotein (NP) containing an affinity tag (rLCMV/Strep-NP) and its use to capture the NP-interactome in infected cells. Our proteomic approach combined with genetics and pharmacological validation assays identified ATPase Na(+)/K(+) transporting subunit alpha 1 (ATP1A1) and prohibitin (PHB) as pro-viral factors. Cell-based assays revealed that ATP1A1 and PHB are involved in different steps of the virus life cycle. Accordingly, we observed a synergistic inhibitory effect on LCMV multiplication with a combination of ATP1A1 and PHB inhibitors. We show that ATP1A1 inhibitors suppress multiplication of Lassa virus and Candid#1, a live-attenuated vaccine strain of Junín virus, suggesting that the requirement of ATP1A1 in virus multiplication is conserved among genetically distantly related mammarenaviruses. Our findings suggest that clinically approved inhibitors of ATP1A1, like digoxin, could be repurposed to treat infections by mammarenaviruses pathogenic for humans.
has issue date	2018-02-20(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1006892
bibo:pmid	29462184
has license	cc0
sha1sum (hex)	efbd0dfc426da5dd25ce29411d6fa37571623773
schema:url	https://doi.org/10.1371/journal.ppat.1006892
resource representing a document's title	Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na(+)/K(+) transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses
has PubMed Central identifier	PMC5834214
has PubMed identifier	29462184
schema:publication	PLoS Pathog
resource representing a document's body	covid:efbd0dfc426da5dd25ce29411d6fa37571623773#body_text
is schema:about of	named entity 'pharmacological' named entity 'combination' named entity 'targeting' named entity 'virus' named entity 'machinery' named entity 'ATPase' named entity 'transporting' named entity 'lymphocytic choriomeningitis virus' covid:arg/efbd0dfc426da5dd25ce29411d6fa37571623773 named entity 'humans' named entity 'encoding' named entity 'ribavirin' named entity 'observed' named entity 'assays' named entity 'lymphocytic choriomeningitis virus' named entity 'inhibitory' named entity 'affinity tag' named entity 'mammarenavirus' named entity 'conserved' named entity 'host-cell' named entity 'validation' named entity 'LCMV' named entity 'infected' named entity 'subunit' named entity 'virus' named entity 'live-attenuated vaccine' named entity 'LCMV' named entity 'genetics' named entity 'Junín virus' named entity 'ATPase' named entity 'synergistic' named entity 'mammarenavirus' named entity 'virus' named entity 'proteomic' named entity 'virus' named entity 'pathogen' named entity 'ATPase' named entity 'Interactome' named entity 'life cycle' named entity 'prohibitin' named entity 'alpha' named entity 'off-label' named entity 'Strep' named entity 'flavagline' named entity 'LCMV' named entity 'infection' named entity 'red channels' named entity 'Germantown, MD' named entity 'interactome' named entity 'cell functions' named entity 'infection' named entity 'Strep' named entity 'siRNA' named entity 'ATP1A1' named entity 'inoculation' named entity 'lysed' named entity 'Cardiac glycoside' named entity 'IKKε' named entity 'host-cell' named entity 'CST' named entity 'chemiluminescent' named entity 'infection' named entity 'siRNA' named entity 'TNF receptor' named entity 'glyceraldehyde-3-phosphate dehydrogenase' named entity 'LCMV' named entity 'immunocompromised' named entity 'formic acid' named entity 'viral hemorrhagic fever' named entity 'helicase' named entity 'cell lysates' named entity 'ion-pumping' named entity 'cell lysates' named entity 'ouabain' named entity 'ouabain'

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