Gene delivery of l-caldesmon protects cytoskeletal cell membrane integrity against adenovirus infection independently of myosin ATPase and actin assembly.
Gene delivery of l-caldesmon protects cytoskeletal cell membrane integrity against adenovirus infection independently of myosin ATPase and actin assembly.
复制标题
L-caldesmon 的基因传递可保护细胞骨架细胞膜的完整性免受腺病毒感染，独立于肌球蛋白 ATP 酶和肌动蛋白组装。
DOI：
10.1152/ajpcell.00530.2003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Moy,AlanB
中科院分区：
文献类型：
--
作者：
Haxhinasto,Kari;Kamath,Anant;Blackwell,Ken;Bodmer,James;VanHeukelom,Jon;English,Anthony;Bai,Er-Wei;Moy,AlanB
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.
