Year: 2014
Type: article
Abstract: Adenovirus's primary receptor, the Coxsackievirus and adenovirus receptor (CAR), has two transmembrane isoforms with differential localization within polarized epithelial cells (CAREx7 (basolateral), CAREx8 (apical)). I hypothesized that each isoform of CAR is degraded at different rates and is regulated by Src-family kinases. Increasing or decreasing the concentration of CAR is predicted to directly alter adenoviral entry. To test this hypothesis, inducible Madin Darby Canine Kidney (MDCK) cell lines either expressing CAREx7, CAREx8, or mCherry, under a doxycycline-inducible promoter were used in pulse-chase structured experiments to calculate the half-lives of these proteins. Alternatively, a polarized model lung epithelium (CaLu-3) treated with Src-kinase inhibitor, PP2, was used to test apical CAREx8 expression and viral transduction. Though CAREx7 and CAREx8 did have varying half-lives (5.1 h, 2.0 h respectively), inhibiting Src-family kinases did not decrease CAREx8 expression at early time points but did diminish adenovirus transduction. These data confirm that Src does not play a role in CAR turnover, but remains critical for adenoviral infection.
Author: Trisha L. Brockman
Institution: Wright State University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2606130024