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Journal of Virology, March 2005, p. 3509-3516, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3509-3516.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Cytokine Osteopontin Modulates the Severity of Rotavirus Diarrhea

Ellen E. Rollo,1 Scott J. Hempson,1 Ajay Bansal,2 Ernest Tsao,2 Iman Habib,1 Susan R. Rittling,3 David T. Denhardt,4 Erich R. Mackow,1,2 and Robert D. Shaw1,2*

Department of Medicine, Northport V.A. Medical Center, Northport,1 Department of Medicine, University Hospital at Stony Brook, Stony Brook, New York,2 Department of Genetics,3 Department of Cellular, Developmental, and Neurobiology, Rutgers University, Piscataway, New Jersey4

Received 25 May 2004/ Accepted 11 October 2004

Osteopontin (OPN) is a sialated phosphoprotein found in tissues and secreted into body fluids. It is an integrin ligand with pleiotropic functions as an extracellular matrix protein in mineralized tissues and a cytokine that is active in cell signaling (A. B. Tuck, C. Hota, S. M. Wilson, and A. F. Chambers, Oncogene 22:1198-1205, 2003). To determine whether OPN may be important in mucosal defense against viral pathogens, we evaluated the OPN response to rotavirus infection and the extent of diarrhea manifested by infected opn null mutant (opn–/–) mice. Reverse transcription-PCR, Northern and Western blots, and immunohistochemical studies of the HT-29 intestinal epithelial cell line and murine intestine were used to evaluate OPN mRNA and product. Intestinal closed loops and diarrheal observations determined disease severity and duration. OPN mRNA levels increased after infection of HT-29 cells, peaking in 4 to 6 h. Infected cultures contained 925 µg of OPN/ml, while for controls the levels were below detection (50 µg/ml). Infection increased OPN mRNA levels in intestinal tissue between 2 and 24 h postinoculation and increased OPN protein in intestinal fluid. The cellular localization of OPN was supranuclear and apical, and responding cells were diffusely distributed on the villus surface. Three days after infection, closed intestinal loops from opn–/– mice contained more fluid than loops from controls, although secretion levels at the onset of illness were similar. Null mutant mice experienced more intense and prolonged diarrhea than controls. Rotavirus infection of intestinal epithelial cells and murine intestine caused marked increases in OPN mRNA levels and secreted OPN protein. OPN-deficient mice suffered prolonged disease.

* Corresponding author. Mailing address: Research Service (151), Northport V.A. Medical Center, Northport, NY 11768. Phone: (631) 261-4400, ext. 2832. Fax: (516) 544-5317. E-mail: rds{at}who.net.

Journal of Virology, March 2005, p. 3509-3516, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3509-3516.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shinohara, M. L., Jansson, M., Hwang, E. S., Werneck, M. B. F., Glimcher, L. H., Cantor, H. (2005). T-bet-dependent expression of osteopontin contributes to T cell polarization. Proc. Natl. Acad. Sci. USA 102: 17101-17106 [Abstract] [Full Text]  


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