About: Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry

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About: Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry 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
has title	Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry
Creator	Côté, Marceline Bo, Yuxia Mulloy, Rory Qiu, Shirley
Source	PMC
abstract	Ebola virus (EBOV) entry requires internalization into host cells and extensive trafficking through the endolysosomal network in order to reach late endosomal/lysosomal compartments that contain triggering factors for viral membrane fusion. These triggering factors include low-pH-activated cellular cathepsin proteases, which cleave the EBOV glycoprotein (GP), exposing a domain which binds to the filoviral receptor, the cholesterol transporter Niemann-Pick C1 (NPC1). Here, we report that trafficking of EBOV to NPC1 requires expression of the homotypic fusion and protein sorting (HOPS) tethering complex as well as its regulator, UV radiation resistance-associated gene (UVRAG). Using an inducible clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, we demonstrated that depletion of HOPS subunits as well as UVRAG impairs entry by all pathogenic filoviruses. UVRAG depletion resulted in reduced delivery of EBOV virions to NPC1(+) cellular compartments. Furthermore, we show that deletion of a domain on UVRAG known to be required for interaction with the HOPS complex results in impaired EBOV entry. Taken together, our studies demonstrate that EBOV requires both expression of and coordination between the HOPS complex and UVRAG in order to mediate efficient viral entry. IMPORTANCE Ebola viruses (EBOV) and other filoviruses cause sporadic and unpredictable outbreaks of highly lethal diseases. The lack of FDA-approved therapeutics, particularly ones with panfiloviral specificity, highlights the need for continued research efforts to understand aspects of the viral life cycle that are common to all filoviruses. As such, viral entry is of particular interest, as all filoviruses must reach cellular compartments containing the viral receptor Niemann-Pick C1 to enter cells. Here, we present an inducible CRISPR/Cas9 method to rapidly and efficiently generate knockout cells in order to interrogate the roles of a broad range of host factors in viral entry. Using this approach, we showed that EBOV entry depends on both the homotypic fusion and protein sorting (HOPS) tethering complex in coordination with UV radiation resistance-associated gene (UVRAG). Importantly, we demonstrate that the HOPS complex and UVRAG are required by all pathogenic filoviruses, representing potential targets for panfiloviral therapeutics.
has issue date	2020-07-30(xsd:dateTime)
bibo:doi	10.1128/jvi.01002-20
bibo:pmid	32493822
has license	cc-by
sha1sum (hex)	eaec614e95fd8ac73fac8dacd8de55a4405511dd
schema:url	https://doi.org/10.1128/jvi.01002-20
resource representing a document's title	Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry
has PubMed Central identifier	PMC7394885
has PubMed identifier	32493822
schema:publication	J Virol
resource representing a document's body	covid:eaec614e95fd8ac73fac8dacd8de55a4405511dd#body_text
is schema:about of	named entity 'complex' named entity 'glycoprotein' named entity 'studies' named entity 'EBOV' named entity 'deletion' named entity 'mediate' named entity 'EBOV' named entity 'viral entry' named entity 'lethal' named entity 'EXPRESSION' named entity 'EBOLA' named entity 'ENTRY' named entity 'PH-' named entity 'REDUCED' named entity 'CELLULAR' named entity 'HOST CELLS' named entity 'VIRAL ENTRY' named entity 'PICK' named entity 'TRAFFICKING' named entity 'ROLES' named entity 'DELETION' named entity 'RAPIDLY' named entity 'NETWORK' named entity 'HOPS' named entity 'DEMONSTRATED' named entity 'GENERATE' named entity 'IMPAIRED' named entity 'Here' named entity 'viral membrane' named entity 'NPC1' named entity 'domain' named entity 'cells' named entity 'unpredictable' named entity 'rapidly' named entity 'Here' named entity 'knockout' named entity 'cleave' named entity 'cells' named entity 'enter' named entity 'order' named entity 'protein' named entity 'UVRAG' named entity 'receptor' named entity 'FDA' named entity 'UVRAG' named entity 'EBOV' named entity 'EBOV' named entity 'virions' named entity 'UVRAG' named entity 'EBOV' named entity 'protein sorting' named entity 'filoviruses' named entity 'EBOV' named entity 'CRISPR' named entity 'cathepsin' named entity 'host cells' named entity 'Ebola' named entity 'Viral Entry' named entity 'UVRAG' named entity 'Niemann-Pick' named entity 'Complex' named entity 'viral entry' named entity 'NPC1' named entity 'glycoprotein' named entity 'PBS' named entity 'PAM' named entity 'homeostasis' named entity 'EBOV' named entity 'deletion mutants' named entity 'VPS18' named entity 'Invitrogen' named entity 'late endosomal' named entity 'University of Illinois' named entity 'pMDG' named entity 'early endosome' named entity 'Immunoblots' named entity 'EBOV' named entity 'CRISPR'

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