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This Article Full Text Full Text (PDF) All Versions of this Article: 287/4/C1125    most recent 00530.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Haxhinasto, K. Articles by Moy, A. B. Search for Related Content PubMed PubMed Citation Articles by Haxhinasto, K. Articles by Moy, A. B.

PROTEIN AND VESICLE TRAFFICKING, CYTOSKELETON

Gene delivery of l-caldesmon protects cytoskeletal cell membrane integrity against adenovirus infection independently of myosin ATPase and actin assembly

¹Department of Internal Medicine and Biomedical Engineering, University of Iowa, Iowa City 52242; ²Department of Mechanical, Aerospace, and Biomedical Engineering, University of Tennessee, Knoxville, Tennessee 37996; and ³Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa 52242

Submitted 26 November 2003 ; accepted in final form 3 June 2004

The cytoskeleton is critical to the viral life cycle. Agents like cytochalasin inhibit viral infections but cannot be used for antiviral therapy because of their toxicity. We report the efficacy, safety, and mechanisms by which gene delivery of human wild-type low-molecular-weight caldesmon (l-CaD) protects cell membrane integrity from adenovirus infection in a DF-1 cell line, an immortalized avian fibroblast that is null for l-CaD. Transfection with an adenovirus (Ad)-controlled construct mediated a dose-dependent decline in transcellular resistance. In accordance with a computational model of cytoskeletal membrane properties, Ad disturbed cell-cell and cell-matrix adhesion and membrane capacitance. Transfection with the Ad-l-CaD construct attenuated adenovirus-mediated loss in transcellular resistance. Quantitation of vinculin-stained plaques revealed an increase in total focal contact mass in monolayers transfected with the Ad-l-CaD construct. Expression of l-CaD protected transcellular resistance through primary effects on membrane capacitance and independently of actin solubility and effects on prestress, as measured by the decline in isometric tension in response to cytochalasin D. Expression of l-CaD exhibited less Trypan blue cell toxicity than cytochalasin, and, unlike cytochalasin, it did not interfere with wound closure or adversely effect transcellular resistance. These findings demonstrate the gene delivery of wild-type human l-CaD as a potentially efficacious and safe agent that inhibits some of the cytopathic effects of adenovirus.

adhesion; motility; computational modeling; focal contact; quantitation

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