About: Opposing activities of IFITM proteins in SARS-CoV-2 infection

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Opposing activities of IFITM proteins in SARS-CoV-2 infection
Creator	Shi, Guoli Zhang, Lizhi Compton, Alex Edu, Yount, Jacob Compton@nih, Alex Gov, Jacob Hall-Stoodley, Luanne Kenney, Adam Kudryashov, Dmitri Kudryashova, Elena Robinson, Richard Yount@osumc,
source	BioRxiv; Medline
abstract	Interferon-induced transmembrane proteins (IFITMs) restrict infections by many viruses, but a subset of IFITMs enhance infections by specific coronaviruses through currently unknown mechanisms. Here we show that SARS-CoV-2 Spike-pseudotyped virus and genuine SARS-CoV-2 infections are generally restricted by expression of human IFITM1, IFITM2, and IFITM3, using both gain- and loss-of-function approaches. Mechanistically, restriction of SARS-CoV-2 occurred independently of IFITM3 S-palmitoylation sites, indicating a restrictive capacity that is distinct from reported inhibition of other viruses. In contrast, the IFITM3 amphipathic helix and its amphipathic properties were required for virus restriction. Mutation of residues within the human IFITM3 endocytosis-promoting YxxΦ motif converted human IFITM3 into an enhancer of SARS-CoV-2 infection, and cell-to-cell fusion assays confirmed the ability of endocytic mutants to enhance Spike-mediated fusion with the plasma membrane. Overexpression of TMPRSS2, which reportedly increases plasma membrane fusion versus endosome fusion of SARS-CoV-2, attenuated IFITM3 restriction and converted amphipathic helix mutants into strong enhancers of infection. In sum, these data uncover new pro- and anti-viral mechanisms of IFITM3, with clear distinctions drawn between enhancement of viral infection at the plasma membrane and amphipathicity-based mechanisms used for endosomal virus restriction. Indeed, the net effect of IFITM3 on SARS-CoV-2 infections may be a result of these opposing activities, suggesting that shifts in the balance of these activities could be coopted by viruses to escape this important first line innate defense mechanism.
has issue date	2020-08-11(xsd:dateTime)
bibo:doi	10.1101/2020.08.11.246678
bibo:pmid	32803197
has license	biorxiv
sha1sum (hex)	1f4081e1da77dc44142b48d3652239f5f6224e35
schema:url	https://doi.org/10.1101/2020.08.11.246678
resource representing a document's title	Opposing activities of IFITM proteins in SARS-CoV-2 infection
has PubMed identifier	32803197
schema:publication	bioRxiv
resource representing a document's body	covid:1f4081e1da77dc44142b48d3652239f5f6224e35#body_text
is schema:about of	named entity 'plasma membrane' named entity 'TMPRSS2' named entity 'SARS-CoV-2' named entity 'Indeed' named entity 'virus' named entity 'enhancement' named entity 'loss-of-function' named entity 'transmembrane proteins' named entity 'human' named entity 'anti-viral' named entity 'independently' named entity 'fusion' named entity 'genuine' named entity 'clear' named entity 'confirmed' named entity 'human' named entity 'amphipathic' named entity 'endosome' named entity 'viruses' named entity 'S-palmitoylation' named entity 'amphipathic' named entity 'IFITM3' named entity 'amphipathic' named entity 'viruses' named entity 'Interferon' named entity 'IFITM3' named entity 'amphipathic' named entity 'virus' named entity 'SARS-CoV-2' named entity 'endocytic' named entity 'SARS-CoV-2' named entity 'proteins' named entity 'IFITM3' named entity 'ACE2' named entity 'cell fusion' named entity 'ACE2' named entity 'infection' named entity 'flash frozen' named entity 'SARS-CoV-2' named entity 'amphipathic' named entity 'causative agent' named entity 'BSL3' named entity 'vesicular stomatitis virus' named entity 'SARS-CoV-2' named entity 'mCherry' named entity 'infection' named entity 'transfection' named entity 'transfected' named entity 'ANOVA' named entity 'enveloped viruses' named entity 'transfecting' named entity 'IFITM3' named entity 'infection' named entity 'pseudotyped' named entity 'Shang' named entity 'Nikon Instruments' named entity 'interferon beta' named entity 'plasmids' named entity 'endogenous' named entity 'influenza virus' named entity 'IAV' named entity 'IFITM3' named entity 'IFITM3' named entity 'SARS-CoV-2' named entity 'cell membrane' named entity 'Luciferase' named entity 'GFP' named entity 'dye' named entity 'Calu-3' named entity 'virus'

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