Vascular cell adhesion molecule-1 augments adenovirus-mediated gene transfer.
We have reported that adenovirus-mediated gene transfer is augmented in the endothelium of atherosclerotic blood vessels. We observed that vascular cell adhesion molecule-1 (VCAM-1) shares some homology with the coxsackievirus and adenovirus receptor. Because VCAM-1 is upregulated on atherosclerotic endothelial cells, we hypothesized that VCAM-1 may act as an auxiliary receptor to augment adenovirus-mediated gene transfer. To test this hypothesis, stable NIH 3T3 cell lines that constitutively express VCAM-1 on the cell surface were generated. Recombinant adenovirus 5 (Ad5), which contains the reporter ss-galactosidase gene, was used to compare Ad5 infection in VCAM-1(+) and parental NIH 3T3 cells. Total ss-galactosidase activity and the number of transgene-positive cells were 6- to 10-fold and 5-fold higher, respectively, in VCAM-1(+) than in VCAM-1(-) cells. Ad5 binding to VCAM-1(+) cells was increased by 3-fold over VCAM-1(-) cells. Soluble VCAM-1 protein, present during infection or viral binding, reduced ss-galactosidase activity in VCAM-1(+) cells in a dose-dependent manner. Taken together, we conclude that VCAM-1 can mediate adenovirus binding and infection. This may explain, in part, the previous finding that adenovirus-mediated gene transfer is augmented in atherosclerotic arteries.
Chu
Y
Y
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Heistad
D
D
Cybulsky
M I
MI
Davidson
B L
BL
D016475:3T3 Cells; D000256:Adenoviridae; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D011817:Rabbits; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism*
D019010:Vascular Cell Adhesion Molecule-1; D001616:beta-Galactosidase