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Journal of Virology, December 2002, p. 12149-12161, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12149-12161.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Noninvasive Bioluminescence Imaging of Herpes Simplex Virus Type 1 Infection and Therapy in Living Mice

Gary D. Luker,1,2 J. Patrick Bardill,3 Julie L. Prior,1,2 Christina M. Pica,1,2 David Piwnica-Worms,1,2 and David A. Leib3,4*

Molecular Imaging Center, Mallinckrodt Institute of Radiology,1 Departments of Molecular Biology and Pharmacology,2 Molecular Microbiology,3 Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 631104

Received 6 June 2002/ Accepted 26 August 2002

Mouse models of herpes simplex virus type 1 (HSV-1) infection provide significant insights into viral and host genes that regulate disease pathogenesis, but conventional methods to determine the full extent of viral spread and replication typically require the sacrifice of infected animals. To develop a noninvasive method for detecting HSV-1 in living mice, we used a strain KOS HSV-1 recombinant that expresses firefly (Photinus pyralis) and Renilla (Renilla reniformis) luciferase reporter proteins and monitored infection with a cooled charge-coupled device camera. Viral infection in mouse footpads, peritoneal cavity, brain, and eyes could be detected by bioluminescence imaging of firefly luciferase. The activity of Renilla luciferase could be imaged after direct administration of substrate to infected eyes but not following the systemic delivery of substrate. The magnitude of bioluminescence from firefly luciferase measured in vivo correlated directly with input titers of recombinant virus used for infection. Treatment of infected mice with valacyclovir, a potent inhibitor of HSV-1 replication, produced dose-dependent decreases in firefly luciferase activity that correlated with changes in viral titers. These data demonstrate that bioluminescence imaging can be used for noninvasive, real-time monitoring of HSV-1 infection and therapy in living mice.

* Corresponding author. Mailing address: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Box 8096, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-2689. Fax: (314) 362-3638. E-mail: Leib{at}vision.wustl.edu.

Journal of Virology, December 2002, p. 12149-12161, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12149-12161.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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