About: A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication

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About: A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication 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	A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication
Creator	Ohlson, Maikke Douglas, Connor Konopka, Genevieve Kumar, Ashwani Xing, Chao Schoggins, John Boys, Ian De, Pamela Eitson, Jennifer Mar, Katrina Mcdougal, Matthew Richardson, R Rivera, La
Source	Medline; PMC
abstract	The endoplasmic reticulum (ER) is an architecturally diverse organelle that serves as a membrane source for the replication of multiple viruses. Flaviviruses, including yellow fever virus, West Nile virus, dengue virus and Zika virus, induce unique single-membrane ER invaginations that house the viral replication machinery1. Whether this virus-induced ER remodelling is vulnerable to antiviral pathways is unknown. Here, we show that flavivirus replication at the ER is targeted by the interferon (IFN) response. Through genome-scale CRISPR screening, we uncovered an antiviral mechanism mediated by a functional gene pairing between IFI6 (encoding IFN-α-inducible protein 6), an IFN-stimulated gene cloned over 30 years ago2, and HSPA5, which encodes the ER-resident heat shock protein 70 chaperone BiP. We reveal that IFI6 is an ER-localized integral membrane effector that is stabilized through interactions with BiP. Mechanistically, IFI6 prophylactically protects uninfected cells by preventing the formation of virus-induced ER membrane invaginations. Notably, IFI6 has little effect on other mammalian RNA viruses, including the related Flaviviridae family member hepatitis C virus, which replicates in double-membrane vesicles that protrude outwards from the ER. These findings support a model in which the IFN response is armed with a membrane-targeted effector that discriminately blocks the establishment of virus-specific ER microenvironments that are required for replication.
has issue date	2018-09-17(xsd:dateTime)
bibo:doi	10.1038/s41564-018-0244-1
bibo:pmid	30224801
has license	no-cc
sha1sum (hex)	529511c62c786dab397b5a3ab3859961a74c8cf8
schema:url	https://doi.org/10.1038/s41564-018-0244-1
resource representing a document's title	A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication
has PubMed Central identifier	PMC6202210
has PubMed identifier	30224801
schema:publication	Nat Microbiol
resource representing a document's body	covid:529511c62c786dab397b5a3ab3859961a74c8cf8#body_text
is schema:about of	named entity 'membrane' named entity 'prophylactically' named entity 'integral' named entity 'chaperone' named entity 'HSP70' named entity 'microenvironments' named entity 'gene' named entity 'yellow fever virus' named entity 'model' named entity 'architecturally' named entity 'interferon' named entity 'MANUSCRIPT' named entity 'IFN' named entity 'STIMULATED' named entity 'ZIKA VIRUS' named entity 'MAMMALIAN' named entity 'FORMATION' named entity 'CLONED' named entity 'RESIDENT' named entity 'INDUCE' named entity 'INCLUDING' named entity 'VIRUS' named entity 'WEST NILE VIRUS' named entity 'RELATED' named entity 'HERE' named entity 'BIP' named entity 'REPLICATES' named entity 'UNINFECTED' named entity 'MODEL' named entity 'INVAGINATIONS' named entity 'PATHWAYS' named entity 'REPLICATION' named entity 'CELLS' named entity 'HEPATITIS C VIRUS' named entity 'THESE' named entity 'MEDIATED' named entity 'CHAPERONE' named entity 'INTERFERON' named entity 'FINDINGS' named entity 'MECHANISM' named entity 'ER-' named entity 'SOURCE' named entity 'RESPONSE' named entity 'STABILIZED' named entity 'VULNERABLE' named entity 'HSP70' named entity 'INDUCED' named entity 'UNCOVERED' named entity 'REPLICATION' named entity 'ARMED' named entity 'REVEAL' named entity 'SUPPORT' named entity 'DIVERSE' named entity 'IFI6' named entity 'EFFECT' named entity 'INTERFERON ' named entity 'OUTWARD' named entity 'DOUBLE' named entity 'AGO' named entity 'GENE' named entity 'RNA VIRUSES' named entity 'FLAVIVIRUS' named entity 'ESTABLISHMENT' named entity 'MEMBRANE' named entity 'PAIRING' named entity 'YELLOW FEVER VIRUS' named entity 'FLAVIVIRUSES' named entity 'ANTIVIRAL' named entity 'PREVENTING'

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