An interaction between penton base and αv integrins plays a minimal role in adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo

T HAUTALA; T GRUNST; A FABREGA; P FREIMUTH; M. J WELSH

doi:10.1038/sj.gt.3300722

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An interaction between penton base and αv integrins plays a minimal role in adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo

Journal article

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An interaction between penton base and αv integrins plays a minimal role in adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo

T HAUTALA, T GRUNST, A FABREGA, P FREIMUTH and M. J WELSH

Gene therapy, Vol.5(9), pp.1259-1264

1998

DOI: 10.1038/sj.gt.3300722

PMID: 9930328

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Abstract

Studies in cultured cell lines have shown that adenovirus infection involves binding of adenovirus fiber to its cell surface receptor and binding of penton base to alpha v integrins. However, much less is known about the role of these interactions in cells that are targets for adenovirus-mediated gene transfer. Earlier work showed that hepatocytes are readily infected by adenovirus, making them an attractive target for gene therapy in several diseases. We found that addition of fiber protein blocked adenovirus infection of primary cultures of hepatocytes. This suggests an important role for fiber and its receptor. However, mutation of the integrin-binding motif in penton base did not inhibit infection of hepatocytes, even though the mutation impaired infection of HeLa cells. Hepatocytes had undetectable amounts of alpha v integrins on their cell surface and showed no specific adherence to vitronectin, the natural substrate of alpha v integrins. Adenovirus with an intact penton base enhanced infection of liver following intravenous injection, but only by three-fold as compared with virus in which the integrin-binding motif was disrupted. These studies suggest that interactions between cell surface integrins and penton base are not required for adenovirus infection of hepatocytes in vitro, but the interaction enhances infection to a small degree in vivo.

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Title: Subtitle: An interaction between penton base and αv integrins plays a minimal role in adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo
Creators: T HAUTALA - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, Iowa City, Iowa, United States
T GRUNST - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, Iowa City, Iowa, United States
A FABREGA - Department of Surgery, University of Iowa College of Medicine, Iowa City, Iowa, United States
P FREIMUTH - Biology Department, Brookhaven National Laboratory, Upton, NY, United States
M. J WELSH - Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Gene therapy, Vol.5(9), pp.1259-1264
DOI: 10.1038/sj.gt.3300722
PMID: 9930328
NLM abbreviation: Gene Ther
ISSN: 0969-7128
eISSN: 1476-5462
Publisher: Nature Publishing Group; Basingstoke
Language: English
Date published: 1998
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
Record Identifier: 9984020645602771

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