This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Graham, K. L. Articles by Coulson, B. S. Search for Related Content PubMed PubMed Citation Articles by Graham, K. L. Articles by Coulson, B. S.

Effects on Rotavirus Cell Binding and Infection of Monomeric and Polymeric Peptides Containing 2ß1 and xß2 Integrin Ligand Sequences

Department of Microbiology and Immunology,¹ Cooperative Research Centre for Vaccine Technology, Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia,² UC Davis Medical Center, University of California-Davis, Sacramento, California³

Received 27 April 2004/ Accepted 28 June 2004

Integrin-using rotaviruses bind MA104 cell surface 2ß1 integrin via the Asp-Gly-Glu (DGE) sequence in virus spike protein VP4 and interact with xß2 integrin during cell entry through outer capsid protein VP7. Infection is inhibited by the 2ß1 ligand Asp-Gly-Glu-Ala (DGEA) and the xß2 ligand Gly-Pro-Arg-Pro (GPRP), and virus-2ß1 binding is increased by 2ß1 activation. In this study, we analyzed the effects of monomers and polymers containing DGEA-, GPRP-, and DGEA-related peptides on rotavirus binding and infection in intestinal (Caco-2) and kidney (MA104) cells and virus binding to recombinant 2ß1. Blockade of rotavirus-cell binding and infection by peptides and anti-2 antibody showed that Caco-2 cell entry is dependent on virus binding to 2ß1 and interaction with xß2. At up to 0.5 mM, monomeric DGEA and DGAA inhibited binding to 2ß1 and infection. At higher concentrations, DGEA and DGAA showed a reduced ability to inhibit virus-cell binding and infection that depended on virus binding to 2ß1 but occurred without alteration in cell surface expression of 2, ß2, or vß3 integrin. This loss of DGEA activity was abolished by genistein treatment and so was dependent on tyrosine kinase signaling. It is proposed that this signaling activated existing cell surface 2ß1 to increase virus-cell attachment and entry. Polymeric peptides containing DGEA and GPRP or GPRP only were inhibitory to SA11 infection at approximately 10-fold lower concentrations than peptide monomers. As polymerization can improve peptide inhibition of virus-receptor interactions, this approach could be useful in the development of inhibitors of receptor recognition by other viruses.

This article has been cited by other articles:

• Halasz, P., Holloway, G., Turner, S. J., Coulson, B. S. (2008). Rotavirus Replication in Intestinal Cells Differentially Regulates Integrin Expression by a Phosphatidylinositol 3-Kinase-Dependent Pathway, Resulting in Increased Cell Adhesion and Virus Yield. J. Virol. 82: 148-160 [Abstract] [Full Text]  
• Andres, A., Donovan, S. M., Kuhlenschmidt, T. B., Kuhlenschmidt, M. S. (2007). Isoflavones at Concentrations Present in Soy Infant Formula Inhibit Rotavirus Infection in Vitro. J. Nutr. 137: 2068-2073 [Abstract] [Full Text]  
• Graham, K. L., O'Donnell, J. A., Tan, Y., Sanders, N., Carrington, E. M., Allison, J., Coulson, B. S. (2007). Rotavirus Infection of Infant and Young Adult Nonobese Diabetic Mice Involves Extraintestinal Spread and Delays Diabetes Onset. J. Virol. 81: 6446-6458 [Abstract] [Full Text]  
• Asokan, A., Hamra, J. B., Govindasamy, L., Agbandje-McKenna, M., Samulski, R. J. (2006). Adeno-Associated Virus Type 2 Contains an Integrin {alpha}5{beta}1 Binding Domain Essential for Viral Cell Entry.. J. Virol. 80: 8961-8969 [Abstract] [Full Text]  
• Graham, K. L., Takada, Y., Coulson, B. S. (2006). Rotavirus spike protein VP5* binds {alpha}2beta1 integrin on the cell surface and competes with virus for cell binding and infectivity.. J. Gen. Virol. 87: 1275-1283 [Abstract] [Full Text]  
• Graham, K. L., Fleming, F. E., Halasz, P., Hewish, M. J., Nagesha, H. S., Holmes, I. H., Takada, Y., Coulson, B. S. (2005). Rotaviruses interact with {alpha}4{beta}7 and {alpha}4{beta}1 integrins by binding the same integrin domains as natural ligands. J. Gen. Virol. 86: 3397-3408 [Abstract] [Full Text]