In vivo imaging of cidofovir treatment of cowpox virus infection

Arthur Goff, Nancy Twenhafel, Aura Garrison, Eric Mucker, James Lawler, Jason Paragas

Research output: Contribution to journalArticle

17 Scopus citations

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 (LD50) 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 25 mg/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.

Original languageEnglish (US)
Pages (from-to)88-98
Number of pages11
JournalVirus Research
Volume128
Issue number1-2
DOIs
StatePublished - Sep 2007

Keywords

  • Biodefense imaging
  • Bioterrorism
  • Cowpox virus
  • Orthopoxvirus
  • Smallpox

ASJC Scopus subject areas

  • Cancer Research
  • Virology
  • Infectious Diseases

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  • Cite this

    Goff, A., Twenhafel, N., Garrison, A., Mucker, E., Lawler, J., & Paragas, J. (2007). In vivo imaging of cidofovir treatment of cowpox virus infection. Virus Research, 128(1-2), 88-98. https://doi.org/10.1016/j.virusres.2007.04.014