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Journal of Virology, December 2000, p. 11304-11310, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Ongoing Viral Replication Is Required for Gammaherpesvirus 68-Induced Vascular Damage

Albert J. Dal Canto, Herbert W. Virgin IV,* and Samuel H. Speck*

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110

Received 1 June 2000/Accepted 11 September 2000

The role of autoimmunity in large-vessel vasculitis in humans remains unclear. We have previously shown that infection of gamma interferon receptor knockout (IFN-gamma R-/-) mice with gammaherpesvirus 68 (gamma HV68) results in severe inflammation of the large elastic arteries that is pathologically similar to the lesions observed in Takayasu's arteritis, the nongranulomatous variant of temporal arteritis, and Kawasaki's disease (K. E. Weck et al., Nat. Med. 3:1346-1353, 1997). Here we define the mechanism of damage to the elastic arteries. We show that there is a persistent productive infection of the media of the large elastic vessels. In addition, we demonstrate that persistent virus replication is necessary for chronic arteritis, since antiviral therapy of mice with established disease resulted in increased survival, clearance of viral antigen from the media of the affected vessel, and dramatic amelioration of arteritic lesions. These data argue that ongoing virus replication, rather than autoimmunity, is the cause of gamma HV68-induced elastic arteritis.


* Corresponding author. Mailing address: Department of Pathology and Immunology, Campus Box 8118, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Phone for Herbert W. Virgin: (314) 362-2993. Fax: (314) 362-4096. E-mail: virgin{at}immunology.wustl.edu. Phone for Samuel H. Speck: (314) 362-0367. Fax: (314) 362-4096. E-mail: speck{at}pathology.wustl.edu.


Journal of Virology, December 2000, p. 11304-11310, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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