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Journal of Virology, January 2006, p. 737-749, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.737-749.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Characterization of Ross River Virus Tropism and Virus-Induced Inflammation in a Mouse Model of Viral Arthritis and Myositis

Thomas E. Morrison,1,2,3 Alan C. Whitmore,3 Reed S. Shabman,1,2,3 Brett A. Lidbury,4 Suresh Mahalingam,4 and Mark T. Heise1,2,3*

Department of Genetics,1 Department of Microbiology and Immunology,2 Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599,3 Viral Arthritis/Asthma Research Group, School of Health Sciences, University of Canberra, Canberra, ACT 2601, Australia4

Received 25 August 2005/ Accepted 22 October 2005

Mosquito-borne alphaviruses are a significant cause of both encephalitic and arthritic disease in humans worldwide. In contrast to the encephalitic alphaviruses, the pathogenesis of alphavirus-induced arthritic disease is not well understood. Utilizing a mouse model of Ross River virus (RRV) disease, we found that the primary targets of RRV infection are bone, joint, and skeletal muscle tissues of the hind limbs in both outbred CD-1 mice and adult C57BL/6J mice. Moreover, histological analyses demonstrated that RRV infection resulted in severe inflammation of these tissues. Characterization of the inflammatory infiltrate within the skeletal muscle tissue identified inflammatory macrophages, NK cells, and CD4+ and CD8+ T lymphocytes. To determine the contribution of the adaptive immune system, the outcome of RRV-induced disease was examined in C57BL/6J RAG-1–/– mice, which lack functional T and B lymphocytes. RAG-1–/– and wild-type mice developed similar disease signs, infiltration of inflammatory macrophages and NK cells, and muscle pathology, suggesting that the adaptive immune response does not play a critical role in the development of disease. These results establish the mouse model of RRV disease as a useful system for the identification of viral and host factors that contribute to alphavirus-induced arthritis and myositis.


* Corresponding author. Mailing address: The Carolina Vaccine Institute, University of North Carolina at Chapel Hill, 827 Mary Ellen Jones Bldg., CB no. 7292, Chapel Hill, NC 27599. Phone: (919) 843-1492. Fax: (919) 843-6924. E-mail: heisem{at}med.unc.edu.


Journal of Virology, January 2006, p. 737-749, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.737-749.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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