Key result
In in vitro models based on Caco-2 cells, both apical and basolateral Ad5 transduction of absorptive enterocytes and M-cells is mediated by binding to the Coxsackievirus and Adenovirus Receptor.
In vitro models demonstrate that the Coxsackievirus and Adenovirus Receptor (CAR) mediates both apical and basolateral adenoviral transduction of enterocytes and M-cells.
CAR targeting may inform intestinal Ad5 vector design; leaves open in vivo translation and clinical utility.
Understanding virus-cell interaction is a key to the design of successful gene delivery vectors. In the present study we investigated Ad5 transduction of enterocytes and M-cells utilizing differentiated Caco-2 cells and cocultures of Caco-2 cells with lymphocytes. Transduction inhibition studies showed that CAR is the major receptor mediating apical and basolateral virus entry in differentiated Caco-2 cells. Integrins and heparan sulfate glycosaminoglycans do not appear to play a significant role. Immunofluorescence localized CAR to sites of cell-cell contact, with staining mostly observed on the cell perimeter. Staining was observed even in nonpermeabilized monolayers, suggesting apical accessibility of the receptor. Cocultures with mouse Peyer's patch lymphocytes or Raji B human lymphocytes were more susceptible to transduction than Caco-2 cells, and the effects were dose-dependent. Similar to Caco-2 cells, CAR and not integrins mediated apical transduction. In conclusion, contrary to other epithelial cell lines, both apical and basolateral transduction of absorptive enterocytes and M-cells is mediated by binding to CAR. The coculture system can be used to study the interactions between M-cells and gene delivery vectors.
No takes yet. Share an insight, caveat, or question.
Kesisoglou et al. (2010) studied Virus-cell interaction in enterocytes and M-cells. Ad5 transduction was evaluated on Receptor mediation of apical and basolateral virus entry. In in vitro models based on Caco-2 cells, both apical and basolateral Ad5 transduction of absorptive enterocytes and M-cells is mediated by binding to the Coxsackievirus and Adenovirus Receptor.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: