About: Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism

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About: Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism
Creator	Kunz, Stefan Xie, Litao Mccray, Paul Dylla, Douglas Michele, Daniel
Source	Medline; PMC
abstract	BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C(50)).
has issue date	2011-04-08(xsd:dateTime)
bibo:doi	10.1186/1479-0556-9-8
bibo:pmid	21477292
has license	cc-by
sha1sum (hex)	f5f53c6d9a31095c447315d0c2ebc42cbcebcfd2
schema:url	https://doi.org/10.1186/1479-0556-9-8
resource representing a document's title	Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism
has PubMed Central identifier	PMC3080791
has PubMed identifier	21477292
schema:publication	Genet Vaccines Ther
resource representing a document's body	covid:f5f53c6d9a31095c447315d0c2ebc42cbcebcfd2#body_text
is schema:about of	named entity 'LCMV' named entity 'β-galactosidase' named entity 'LCMV' named entity 'animals' named entity 'FIV' named entity 'Methods' named entity 'vectors' named entity 'These' named entity 'vector' named entity 'affinity' named entity 'unique' named entity 'ALTERING' covid:arg/f5f53c6d9a31095c447315d0c2ebc42cbcebcfd2 named entity 'EITHER' named entity 'GENE TRANSFER' named entity 'ABUNDANT' named entity 'FELINE IMMUNODEFICIENCY VIRUS' named entity 'EVALUATED' named entity 'LOW' named entity 'LOWER' named entity 'LATE' named entity 'EXPRESSED' named entity 'CHANGE' named entity 'INTERACTIONS' named entity 'DETECTED' named entity 'UNIQUE' named entity 'TISSUE' named entity 'MUTANT' named entity 'TO BIND TO' named entity 'ENGINEERED' named entity 'TROPISMS' named entity 'POINT MUTATION' named entity 'BACKGROUND' named entity 'ALTER' named entity 'THEIR' named entity 'STRAINS' named entity 'NON-' named entity 'LUCIFERASE ASSAYS' named entity 'TISSUE TROPISM' named entity 'SURFACES' named entity 'MAY HAVE' named entity 'STAINING' named entity 'METHODS' named entity 'DYSTROGLYCAN' named entity 'VECTOR' named entity 'MICE' named entity 'REGULATED' named entity 'IMAGING' named entity 'GLYCOPROTEINS' named entity 'FIV' named entity 'CONCLUSIONS' named entity 'VECTORS' named entity 'RECEPTOR' named entity 'FOLLOWING' named entity 'NEONATAL' named entity 'ADULT' named entity 'LOW PH' named entity 'LENTIVIRUS' named entity 'APPLICATIONS' named entity 'TRANSDUCTION' named entity 'PRIMATE' named entity 'CARDIOMYOCYTE' named entity 'RECEPTORS' named entity 'LENTIVIRUS' named entity 'AFFINITY' named entity 'RECEPTOR' named entity 'LCMV' named entity 'IN VIVO' named entity 'TISSUE TROPISM' named entity 'CELL' named entity 'IN VITRO' named entity 'FUSE' named entity 'GALACTOSIDASE' named entity 'GLYCOPROTEIN' named entity 'DELIVERY' named entity 'UNKNOWN' named entity 'DERIVED'

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