Noninvasive bioluminescence imaging of herpes simplex virus type 1 infection and therapy in living mice.
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.
Luker
Gary D
GD
Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Bardill
J Patrick
JP
Prior
Julie L
JL
Pica
Christina M
CM
Piwnica-Worms
David
D
Leib
David A
DA
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter / Q000187:drug effects; D006561:Herpes Simplex / Q000188:drug therapy / Q000209:etiology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D016849:Keratitis, Herpetic / Q000821:virology; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D051379:Mice; D009928:Organ Specificity; D013997:Time Factors; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000998:Antiviral Agents; D008156:Luciferases; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir