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Journal of Virology, October 2000, p. 9294-9299, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Sindbis-Group Alphavirus Replication in Periosteum and Endosteum of Long Bones in Adult Mice

Mark T. Heise,* Dennis A. Simpson,dagger and Robert E. Johnston

Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290

Received 14 February 2000/Accepted 28 June 2000

Several alphaviruses, including the Sindbis-group viruses, Ross River virus, O'nyong-nyong virus, and Chikungunya virus, are associated with outbreaks of acute and persistent arthralgia and arthritis in humans. Mechanisms underlying alphavirus-induced arthralgia and arthritis are not clearly understood, though direct viral replication within or around the affected joints is thought to contribute to disease. S.A.AR86 is a Sindbis-group alphavirus closely related to the arthralgia-associated Ockelbo and GirdwoodS.A viruses. Following inoculation with S.A.AR86 derived from a molecular clone, infectious virus was isolated from bone and joint tissue 1 to 6 days postinfection. Studies using either in situ hybridization or S.A.AR86-derived double promoter viruses and replicons expressing green fluorescent protein localized sites of viral replication to the periosteum, tendons, and endosteum within the epiphyses of the long bones adjacent to articular joints. These results demonstrate that alphaviruses associated with arthralgia in humans replicate within bone-associated connective tissue adjacent to articular joints in an adult mouse model.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Campus Box 7290, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290. Phone: (919) 966-4026. Fax: (919) 843-6924. E-mail: heisem{at}med.unc.edu.

dagger Present address: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295.

Journal of Virology, October 2000, p. 9294-9299, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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