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Journal of Virology, June 2007, p. 6446-6458, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.00205-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Rotavirus Infection of Infant and Young Adult Nonobese Diabetic Mice Involves Extraintestinal Spread and Delays Diabetes Onset

Kate L. Graham,^, Joanne A. O'Donnell,^, Yan Tan,^¶ Natalie Sanders, Emma M. Carrington, Janette Allison, and Barbara S. Coulson^*

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

Received 29 January 2007/ Accepted 3 April 2007

Rotaviruses have been implicated as a possible viral trigger for exacerbations in islet autoimmunity, suggesting they might modulate type 1 diabetes development. In this study, the ability of rotavirus strain RRV to infect the pancreas and affect insulitis and diabetes was examined in nonobese diabetic (NOD) mice, an experimental model of type 1 diabetes. Mice were inoculated either orally or intraperitoneally as infants or young adults. In infant mice inoculated orally, rotavirus antigen was detected in pancreatic macrophages outside islets and infectious virus was found in blood cells, pancreas, spleen, and liver. Extraintestinal RRV spread and pancreatic presence of infectious virus also occurred in intraperitoneally inoculated infant and adult mice. The initiation of insulitis was unaltered by infection. The onset of diabetes was delayed in infant mice inoculated orally and infant and adult mice inoculated intraperitoneally. In contrast, adult mice inoculated orally showed no evidence of pancreatic RRV, the lowest rate of detectable RRV replication, and no diabetes modulation. Thus, the ability of RRV infection to modulate diabetes development in infant and young adult NOD mice was related to the overall extent of detectable virus replication and the presence of infectious virus extraintestinally, including in the pancreas. These studies show that RRV infection of infant and young adult NOD mice provides significant protection against diabetes. As these findings do not support the hypothesis that rotavirus triggers autoimmunity related to type 1 diabetes, further research is needed to resolve this issue.

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* 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

Published ahead of print on 11 April 2007.

Present address: St. Vincent's Institute, Fitzroy, Victoria 3065, Australia.

K.L.G. and J.A.O. contributed equally to this work.

Present address: CSL Limited, 45 Poplar Road, Parkville, Victoria 3052, Australia.

^¶ Present address: Department of Dentistry, The University of Melbourne, Victoria 3010, Australia.

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Journal of Virology, June 2007, p. 6446-6458, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.00205-07
Copyright © 2007, 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]