About: The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases 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	The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases
Creator	Perlman, Stanley Li, Kun Frieman, Matthew Gallagher, Tom Hantak, Michael Mccray, Paul Earnest, James
Source	Medline; PMC
abstract	Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an in vivo CoV infection model, we used recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs, thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4 vectors co-expressed small RNAs silencing Cd9 or Tmprss2, the animals were significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated robust in vivo MERS-CoV infection of mouse lungs. Furthermore, the S proteins of virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character, suggesting that CD9 is a selective agent in the evolution of CoV virulence.
has issue date	2017-07-31(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1006546
bibo:pmid	28759649
has license	cc-by
sha1sum (hex)	0749cab30d660b29d52b5346b02773a3f36fda0d
schema:url	https://doi.org/10.1371/journal.ppat.1006546
resource representing a document's title	The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases
has PubMed Central identifier	PMC5552337
has PubMed identifier	28759649
schema:publication	PLoS Pathog
resource representing a document's body	covid:0749cab30d660b29d52b5346b02773a3f36fda0d#body_text
is schema:about of	named entity 'binding' named entity 'rapidly' named entity 'activated' named entity 'MERS-CoV' named entity 'infection' named entity 'Infection' named entity 'BOUND' named entity 'SCAFFOLDING' named entity 'ANIMALS' named entity 'CONDENSATION' named entity 'FOUND' named entity 'BINDING' named entity 'TRANSMEMBRANE' named entity 'EFFICIENT' named entity 'CD9' named entity 'ENTRY' named entity 'PROTEOLYTIC' named entity 'RECOMBINANT ADENOVIRUS' named entity 'EXPRESSED' named entity 'SELECTIVE AGENT' named entity 'CELLS' named entity 'CD81' named entity 'RAPIDLY' named entity 'VIRAL' named entity 'RAD5' named entity 'KNOWN' named entity 'FOLLOWED BY' named entity 'ALLOWED' named entity 'MEMBER' named entity 'VIRULENCE' named entity 'EVALUATE' named entity 'ON CELL' named entity 'TRAFFICKED' named entity 'INFECTION MODEL' named entity 'RECEPTOR' named entity 'IDENTIFIED' named entity 'BUT' named entity 'PROTEASES' named entity 'HOST CELL' named entity 'SMALL' named entity 'TETRASPANINS' named entity 'RNAS' named entity 'COVS' named entity 'SPIKE' named entity 'MUCH' named entity 'TETRASPANIN' named entity 'MERS' named entity 'RECEPTORS' named entity 'CORONAVIRUS' named entity 'INFECTION' named entity 'CD9' named entity 'ADENOVIRUS 5' named entity 'MERS-COV' named entity 'HOLD' named entity 'ENDOSOMES' named entity 'SILENCING' named entity 'USED' named entity 'SUSCEPTIBLE' named entity 'INDICATING' named entity 'HUMAN' named entity 'CELL' named entity 'VIRULENT' named entity 'EARLY' named entity 'DPP4' named entity 'CHARACTER' named entity 'TO BE CLEAVED' named entity 'CELL MEMBRANE' named entity 'THESE' named entity 'ACQUIRED' named entity 'ADAPTED' named entity 'KNOCKOUT CELL' named entity 'TYPE II' named entity 'LATER' named entity 'ROBUST' named entity 'SURFACE'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software