title: In vivo imaging of cidofovir treatment of cowpox virus infection.
abstract: Variola virus and other members of the genus Orthopoxviruses constitute a prominent bioterrorism and public health threat. Treatment with the anti-viral drug cidofovir inhibits replication of orthopoxviruses in vitro and in vivo. In this study, we visualized the effect of cidofovir on viral kinetics in orthopoxvirus infected mice by using whole-body fluorescence imaging (FI). We engineered a cowpox virus (CPV) expressing the enhanced green fluorescent protein (GFP). Single-step growth curves and calculated 50% lethal doses (LD(50)) of wild-type CPX (Wt-CPV) and GFP-expressing CPX (GFP-CPV) were comparable. Whole-body FI first detected GFP fluorescence in the mesenteric tissue of untreated animals on post-infection day (PID) 1. On PID 3 GFP signal was detected throughout the mesentery, in all abdominal organs by PID 5 and in most major organs, except for the heart and brain by PID 6. Infected animals treated with 25mg/kg of cidofovir also began showing signs of viral replication on PID 1, however, the fluorescent signal was limited only to discrete foci throughout the course of the infection. This work describes the first use of an established Orthopox model of infection to evaluate drug efficacy and track virus progression on a macroscopic level.
authors.affiliation: Virology Division, United States Army Medical Research Institute for Infectious Diseases, MD 21702-5011, USA. Arthur.Goff@det.amedd.army.mil
authors.forename: Arthur
authors.initials: A
authors.lastname: Goff
authors.forename: Nancy
authors.initials: N
authors.lastname: Twenhafel
authors.forename: Aura
authors.initials: A
authors.lastname: Garrison
authors.forename: Eric
authors.initials: E
authors.lastname: Mucker
authors.forename: James
authors.initials: J
authors.lastname: Lawler
authors.forename: Jason
authors.initials: J
authors.lastname: Paragas
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023482:Bioterrorism; D002522:Chlorocebus aethiops; D000077404:Cidofovir; D015605:Cowpox / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D015608:Cowpox virus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004261:DNA Replication; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011995:Recombination, Genetic; D012899:Smallpox / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D016896:Treatment Outcome; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D049452:Green Fluorescent Proteins; D003596:Cytosine; D000077404:Cidofovir