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Journal of Virology, January 2008, p. 148-160, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01980-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Rotavirus Replication in Intestinal Cells Differentially Regulates Integrin Expression by a Phosphatidylinositol 3-Kinase-Dependent Pathway, Resulting in Increased Cell Adhesion and Virus Yield{triangledown}

Peter Halasz, Gavan Holloway, Stephen J. Turner, and Barbara S. Coulson*

Department of Microbiology and Immunology, The University of Melbourne, Victoria 3010, Australia

Received 10 September 2007/ Accepted 10 October 2007

Changes in the interactions between intestinal cells and their surrounding environment during virus infection have not been well documented. The growth and survival of intestinal epithelial cells, the main targets of rotavirus infection, are largely dependent on the interaction of cell surface integrins with the extracellular matrix. In this study, we detected alterations in cellular integrin expression following rotavirus infection, identified the signaling components required, and analyzed the subsequent effects on cell binding to the matrix component collagen. After rotavirus infection of intestinal cells, expression of {alpha}2β1 and β2 integrins was up-regulated, whereas that of {alpha}Vβ3, {alpha}Vβ5, and {alpha}5β1 integrins, if present, was down-regulated. This differential regulation of integrins was reflected at the transcriptional level. It was unrelated to the use of integrins as rotavirus receptors, as both integrin-using and integrin-independent viruses induced integrin regulation. Using pharmacological agents that inhibit kinase activity, integrin regulation was shown to be dependent on phosphatidylinositol 3-kinase (PI3K) but independent of the activities of the mitogen-activated protein kinases p38 and ERK1/2, and cyclooxygenase-2. Replication-dependent activation of the PI3K/Akt pathway was observed following infection of intestinal and nonintestinal cell lines. Rotavirus activation of PI3K was important for regulation of {alpha}2β1 expression. Blockade of integrin regulation by PI3K inhibition led to decreased adherence of infected intestinal cells to collagen and a concomitant decrease in virus titer. These findings indicate that rotavirus-induced PI3K activation causes regulation of integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Gate 11, Royal Parade, The University of Melbourne, Melbourne, Victoria 3010, Australia. Phone: 61 3 8344 8823. Fax: 61 3 9347 1540. E-mail: barbarac{at}unimelb.edu.au

{triangledown} Published ahead of print on 17 October 2007.

Journal of Virology, January 2008, p. 148-160, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01980-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Graham, K. L., Sanders, N., Tan, Y., Allison, J., Kay, T. W. H., Coulson, B. S. (2008). Rotavirus Infection Accelerates Type 1 Diabetes in Mice with Established Insulitis. J. Virol. 82: 6139-6149 [Abstract] [Full Text]  
  • Seo, N.-S., Zeng, C. Q.-Y., Hyser, J. M., Utama, B., Crawford, S. E., Kim, K. J., Hook, M., Estes, M. K. (2008). Inaugural Article: Integrins {alpha}1{beta}1 and {alpha}2{beta}1 are receptors for the rotavirus enterotoxin. Proc. Natl. Acad. Sci. USA 105: 8811-8818 [Abstract] [Full Text]  


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