About: Engineered receptors for human cytomegalovirus that are orthogonal to normal human biology

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About: Engineered receptors for human cytomegalovirus that are orthogonal to normal human biology 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	Engineered receptors for human cytomegalovirus that are orthogonal to normal human biology
Creator	Park, Jihye Choi, Hannah Oberstein, Adam Asghar, Ali Dallas Heredia Id, Jeremiah Gill Id, Kevin Id, Aghajani Prockoid, Erik
Source	Medline; PMC
abstract	A trimeric glycoprotein complex on the surface of human cytomegalovirus (HCMV) binds to platelet-derived growth factor (PDGF) receptor α (PDGFRα) to mediate host cell recognition and fusion of the viral and cellular membranes. Soluble PDGFRα potently neutralizes HCMV in tissue culture, and its potential use as an antiviral therapeutic has the benefit that any escape mutants will likely be attenuated. However, PDGFRα binds multiple PDGF ligands in the human body as part of developmental programs in embryogenesis and continuing through adulthood. Any therapies with soluble receptor therefore come with serious efficacy and safety concerns, especially for the treatment of congenital HCMV. Soluble virus receptors that are orthogonal to human biology might resolve these concerns. This engineering problem is solved by deep mutational scanning on the D2-D3 domains of PDGFRα to identify variants that maintain interactions with the HCMV glycoprotein trimer in the presence of competing PDGF ligands. Competition by PDGFs is conformation-dependent, whereas HCMV trimer binding is independent of proper D2-D3 conformation, and many mutations at the receptor-PDGF interface are suitable for functionally separating trimer from PDGF interactions. Purified soluble PDGFRα carrying a targeted mutation succeeded in displaying wild type affinity for HCMV trimer with a simultaneous loss of PDGF binding, and neutralizes trimer-only and trimer/pentamer-expressing HCMV strains infecting fibroblasts or epithelial cells. Overall, this work makes important progress in the realization of soluble HCMV receptors for clinical application.
has issue date	2020-06-19(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1008647
bibo:pmid	32559251
has license	cc-by
sha1sum (hex)	0072fc08bed8a135390cbf98641a47736d6c93e1
schema:url	https://doi.org/10.1371/journal.ppat.1008647
resource representing a document's title	Engineered receptors for human cytomegalovirus that are orthogonal to normal human biology
has PubMed Central identifier	PMC7329128
has PubMed identifier	32559251
schema:publication	PLoS Pathog
resource representing a document's body	covid:0072fc08bed8a135390cbf98641a47736d6c93e1#body_text
is schema:about of	named entity 'receptors' named entity 'growth factor' named entity 'trimer' named entity 'programs' named entity 'Overall' named entity 'cellular membranes' named entity 'maintain' named entity 'solved' named entity 'PDGF BINDING' named entity 'ITS' named entity 'MULTIPLE' named entity 'HCMV' named entity 'HUMAN BIOLOGY' named entity 'WILD TYPE' named entity 'DEVELOPMENTAL' named entity 'tissue culture' named entity 'affinity' named entity 'This' named entity 'PDGFRα' named entity 'problem' named entity 'BSA' named entity 'protein' named entity 'antiviral drugs' named entity 'nanomolar' named entity 'PDGFRα' named entity 'HCMV' named entity 'biochemical' named entity 'room temperature' named entity 'serum' named entity 'transmembrane domain' named entity 'transfection' named entity 'streptomycin sulfate' named entity 'nuclei' named entity 'pH 3' named entity 'Enhancers' named entity 'Schrödinger, LLC' named entity 'trimer' named entity 'clone' named entity 'GFP' named entity 'trimer' named entity 'Virion' named entity 'PDGFRα' named entity 'hydrophobic' named entity 'PDGFRα' named entity 'physiological' named entity 'PDGFRα' named entity 'Cell Signaling Technology' named entity 'sfGFP' named entity 'potency' named entity 'embryogenesis' named entity 'PDGFRα' named entity 'fluorescent protein' named entity 'folded structure' named entity 'PDGFRα' named entity 'PDGFRα' named entity 'primers' named entity 'kDa' named entity 'nonsynonymous' named entity 'dead cells' named entity 'supernatant' named entity 'Fc region' named entity 'C-terminal' named entity 'RNA' named entity 'ligated' named entity 'HCMV' named entity 'FcRn' named entity 'plasmid' named entity 'plasmid' named entity 'SSM' named entity 'correlation' named entity 'transfection' named entity 'cDNA' named entity 'Thomas Shenk' named entity 'antibody-dependent cell-mediated cytotoxicity'

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