Document Detail


Interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.
MedLine Citation:
PMID:  22347482     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Application of human adenovirus type 5 (Ad5) derived vectors for cancer gene therapy has been limited by the poor cell surface expression, on some tumor cell types, of the primary Ad5 receptor, the coxsackie-adenovirus-receptor (CAR), as well as the accumulation of Ad5 in the liver following interaction with blood coagulation factor X (FX) and subsequent tethering of the FX-Ad5 complex to heparan sulfate proteoglycan (HSPG) on liver cells. As an alternative vector, mouse adenovirus type 1 (MAV-1) is particularly attractive, since this non-human adenovirus displays pronounced endothelial cell tropism and does not use CAR as a cellular attachment receptor. We here demonstrate that MAV-1 uses cell surface heparan sulfate proteoglycans (HSPGs) as primary cellular attachment receptor. Direct binding of MAV-1 to heparan sulfate-coated plates proved to be markedly more efficient compared to that of Ad5. Experiments with modified heparins revealed that the interaction of MAV-1 to HSPGs depends on their N-sulfation and, to a lesser extent, 6-O-sulfation rate. Whereas the interaction between Ad5 and HSPGs was enhanced by FX, this was not the case for MAV-1. A slot blot assay demonstrated the ability of MAV-1 to directly interact with FX, although the amount of FX complexed to MAV-1 was much lower than observed for Ad5. Analysis of the binding of MAV-1 and Ad5 to the NCI-60 panel of different human tumor cell lines revealed the preference of MAV-1 for ovarian carcinoma cells. Together, the data presented here enlarge our insight into the HSPG receptor usage of MAV-1 and support the development of an MAV-1-derived gene vector for human cancer therapy.
Authors:
Liesbeth Lenaerts; Wim van Dam; Leentje Persoons; Lieve Naesens
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-07
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-07-31     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e31454     Citation Subset:  IM    
Affiliation:
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adenoviridae / metabolism*
Animals
Cancer Vaccines
Cell Line, Tumor
Genetic Vectors
Heparan Sulfate Proteoglycans / metabolism*
Humans
Mice
Protein Binding
Receptors, Virus*
Chemical
Reg. No./Substance:
0/Cancer Vaccines; 0/Heparan Sulfate Proteoglycans; 0/Receptors, Virus; 0/adenovirus receptor
Comments/Corrections

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


Previous Document:  Phylogeographic study of Apodemus ilex (Rodentia: Muridae) in Southwest China.
Next Document:  Plasma cell-free DNA levels are elevated in acute Puumala hantavirus infection.