Document Detail


Cell Membrane-associated heparan sulfate is a receptor for prototype foamy virus in human, monkey, and rodent cells.
MedLine Citation:
PMID:  22434139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Foamy viruses (FVs) (spumaretroviruses) are good alternative to retroviruses as gene therapy vector. Despite four decades since the discovery of FV, its receptor molecule is still unknown. FV vector transduction of human CD34(+) cells was inhibited by culture with fibronectin. Because fibronectin contains heparin-binding domain, the interactions of fibronectin with heparan sulfate (HS) on cells might be inhibitory to FV transduction. These observations led us to investigate whether HS is a receptor for FV. Two mutant CHO cell lines (but not parental wild type) lacking cell surface HS but not chondroitin sulfate (CS) were largely resistant to FV attachment and transduction. Inhibition of HS expression using enzymes or chemicals greatly reduced FV transduction in human, monkey, and rodent cells. Raji cells, which lack HS and were largely resistant to FV, were rendered more permissive through ectopic expression of syndecan-1, which contains HS. In contrast, mutant syndecan-1-expressing cells were largely resistant to FV. Our findings indicate that cellular HS is a receptor for FV. Identifying FV receptor will enable better understanding of its entry process and optimal use as gene therapy vector to treat inherited and pathogenic diseases.
Authors:
Md Nasimuzzaman; Derek A Persons
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-20
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  20     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-11-07     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1158-66     Citation Subset:  IM    
Affiliation:
Division of Experimental Hematology, Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. Md.Nasimuzzaman@stjude.org
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Cell Line
Cell Membrane / chemistry*,  metabolism
Cricetinae
Down-Regulation
Fibronectins / metabolism
Gene Expression
Haplorhini
Heparitin Sulfate / biosynthesis,  metabolism*
Humans
Mice
Polysaccharide-Lyases / metabolism
Receptors, Virus / metabolism*
Rodentia
Spumavirus / metabolism*
Syndecan-1 / genetics,  metabolism
Transduction, Genetic
Grant Support
ID/Acronym/Agency:
P01HL053749/HL/NHLBI NIH HHS; U54HL070590/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibronectins; 0/Receptors, Virus; 0/Syndecan-1; 9050-30-0/Heparitin Sulfate; EC 4.2.2.-/Polysaccharide-Lyases; EC 4.2.2.8/heparitinsulfate lyase
Comments/Corrections
Comment In:
Mol Ther. 2012 Jun;20(6):1105-7   [PMID:  22652999 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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