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Journal of Virology, February 2004, p. 1564-1574, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1564-1574.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Astrovirus-Induced Synthesis of Nitric Oxide Contributes to Virus Control during Infection

Matthew D. Koci,1,2 Laura A. Kelley,3 Diane Larsen,4 and Stacey Schultz-Cherry2*

Department of Pathology, University of Georgia, Athens, Georgia 30602,1 Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin 53706,2 Southeast Poultry Research Laboratory, USDA Agricultural Research Station, Athens, Georgia 30605,3 Merial Limited, Duluth, Georgia 30096-46404

Received 17 June 2003/ Accepted 9 October 2003

Astrovirus is one of the major causes of infant and childhood diarrhea worldwide. Our understanding of astrovirus pathogenesis trails behind our knowledge of its molecular and epidemiologic properties. Using a recently developed small-animal model, we investigated the mechanisms by which astrovirus induces diarrhea and the role of both the adaptive and innate immune responses to turkey astrovirus type-2 (TAstV-2) infection. Astrovirus-infected animals were analyzed for changes in total lymphocyte populations, alterations in CD4+/CD8+ ratios, production of virus-specific antibodies (Abs), and macrophage activation. There were no changes in the numbers of circulating or splenic lymphocytes or in CD4+/CD8+ ratios compared to controls. Additionally, there was only a modest production of virus-specific Abs. However, adherent spleen cells from infected animals produced more nitric oxide (NO) in response to ex vivo stimulation with lipopolysaccharide. In vitro analysis demonstrated that TAstV-2 induced macrophage production of inducible nitric oxide synthase. Studies using NO donors and inhibitors in vivo demonstrated, for the first time, that NO inhibited astrovirus replication. These studies suggest that NO is important in limiting astrovirus replication and are the first, to our knowledge, to describe the potential role of innate immunity in astrovirus infection.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, 1300 University Ave., Room 417 SMI, Madison, WI 53706. Phone: (608) 265-6462. Fax: (608) 262-8418. E-mail: slschul2{at}wisc.edu.

Journal of Virology, February 2004, p. 1564-1574, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1564-1574.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Moser, L. A., Carter, M., Schultz-Cherry, S. (2007). Astrovirus Increases Epithelial Barrier Permeability Independently of Viral Replication. J. Virol. 81: 11937-11945 [Abstract] [Full Text]  


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