Integrin-Mediated Signaling Events Involved in Adenovirus Internalization and Cell Motility

Previous studies in our laboratory showed that human adenoviruses use integrins αvß3 and αvß5 to promote internalization. In recent studies, we investigated the mechanisms by which αv integrins promote viral uptake by cells. We found that several signaling molecules, including focal adhesion kinase and phosphatidylinositol-3-kinase, become phosphorylated during interaction of the adenovirus penton base with αv integrins. Kinase phosphorylation is also associated with increased activation of phosphatidylinositol-3-kinase. Pharmacologic agents and genetic dysregulation of phosphatidylinositol-3-kinase blocked internalization of adenovirus and infection yet had no effect on integrin-mediated cell adhesion or motility, a cellular process regulated by the Erk1/Erk2 MAP kinase pathway. These studies indicate that integrin ligation by the extracellular matrix or by viral proteins can lead to the engagement of distinct signaling pathways that promote viral endocytosis or cell movement (Fig. 1).