title: In vivo imaging systems (IVIS) detection of a neuro-invasive encephalitic virus.
abstract: Modern advancements in imaging technology encourage further development and refinement in the way viral research is accomplished. Initially proposed by Russel and Burch in Hume's 3Rs (replacement, reduction, refinement), the utilization of animal models in scientific research is under constant pressure to identify new methodologies to reduce animal usage while improving scientific accuracy and speed. A major challenge to Hume's principals however, is how to ensure the studies are statistically accurate while reducing animal disease morbidity and overall numbers. Vaccine efficacy studies currently require a large number of animals in order to be considered statistically significant and often result in high morbidity and mortality endpoints for identification of immune protection. We utilized in vivo imaging systems (IVIS) in conjunction with a firefly bioluminescent enzyme to progressively track the invasion of the central nervous system (CNS) by an encephalitic virus in a murine model. Typically, the disease progresses relatively slowly, however virus replication is rapid, especially within the CNS, and can lead to an often, lethal outcome. Following intranasal infection of the mice with TC83-Luc, an attenuated Venezuelan equine encephalitis virus strain modified to expresses a luciferase gene; we are able to visualize virus replication within the brain at least three days before the development of clinical disease symptoms. Utilizing CNS invasion as a key encephalitic disease development endpoint we are able to quickly identify therapeutic and vaccine protection against TC83-Luc infection before clinical symptoms develop. With IVIS technology we are able to demonstrate the rapid and accurate testing of drug therapeutics and vaccines while reducing animal numbers and morbidity.
authors.affiliation: Experimental Pathology, University of Texas Medical Branch, TX, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Poussard
authors.forename: Michael
authors.initials: M
authors.lastname: Patterson
authors.forename: Katherine
authors.initials: K
authors.lastname: Taylor
authors.forename: Alexey
authors.initials: A
authors.lastname: Seregin
authors.forename: Jeanon
authors.initials: J
authors.lastname: Smith
authors.forename: Jennifer
authors.initials: J
authors.lastname: Smith
authors.forename: Milagros
authors.initials: M
authors.lastname: Salazar
authors.forename: Slobodan
authors.initials: S
authors.lastname: Paessler
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D002490:Central Nervous System / Q000821:virology*; D004666:Encephalitis Virus, Venezuelan Equine / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D014613:Vaccines, Attenuated / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines / Q000737:chemistry / Q000276:immunology; D014779:Virus Replication
chemical_list: D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D049409:Luciferases, Firefly