Interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.

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 interac...

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Autores principales:	Liesbeth Lenaerts, Wim van Dam, Leentje Persoons, Lieve Naesens
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7cc20047ec544fa9ab801ba14fdedf9a
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spelling	oai:doaj.org-article:7cc20047ec544fa9ab801ba14fdedf9a2021-11-18T07:28:45ZInteraction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.1932-620310.1371/journal.pone.0031454https://doaj.org/article/7cc20047ec544fa9ab801ba14fdedf9a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22347482/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Application 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.Liesbeth LenaertsWim van DamLeentje PersoonsLieve NaesensPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31454 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liesbeth Lenaerts Wim van Dam Leentje Persoons Lieve Naesens Interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.
description	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.
format	article
author	Liesbeth Lenaerts Wim van Dam Leentje Persoons Lieve Naesens
author_facet	Liesbeth Lenaerts Wim van Dam Leentje Persoons Lieve Naesens
author_sort	Liesbeth Lenaerts
title	Interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.
title_short	Interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.
title_full	Interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.
title_fullStr	Interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.
title_full_unstemmed	Interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.
title_sort	interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/7cc20047ec544fa9ab801ba14fdedf9a
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Interaction between mouse adenovirus type 1 and cell surface heparan sulfate proteoglycans.

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