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J Virol, March 1998, p. 2055-2061, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Adenovirus Endocytosis via alpha v Integrins Requires Phosphoinositide-3-OH Kinase

Erguang Li, Dwayne Stupack, Richard Klemke, David A. Cheresh, and Glen R. Nemerow*

Department of Immunology, The Scripps Research Institute, La Jolla, California 92037

Received 29 August 1997/Accepted 26 November 1997

Integrins mediate cell adhesion and motility on the extracellular matrix, yet they also promote viral attachment and/or entry. Evidence is presented that adenovirus internalization by alpha v integrins requires activation of phosphoinositide-3-OH kinase (PI3K), whereas alpha v integrin-mediated cell motility depends on the ERK1/ERK2 mitogen-activated protein kinase pathway. Interaction of adenovirus with alpha v integrins induced activation of PI3K. Pharmacologic or genetic disruption of endogenous PI3K activity blocked adenovirus internalization and virus-mediated gene delivery yet had no effect on integrin-mediated cell adhesion or motility. Therefore, integrin ligation engages distinct signaling pathways that promote viral endocytosis or cell movement.

* Corresponding author. Mailing address: Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-8072. Fax: (619) 784-8472. E-mail: gnemerow{at}scripps.edu.




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