title: Rapid, non-invasive imaging of alphaviral brain infection: reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals.
abstract: Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume's 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion.
authors: Department of Pathology, Preclinical Studies Core at Galveston National Laboratory, USA.
authors: Michael
authors: M
authors: Patterson
authors: Allison
authors: A
authors: Poussard
authors: Katherine
authors: K
authors: Taylor
authors: Alexey
authors: A
authors: Seregin
authors: Jeanon
authors: J
authors: Smith
authors: Bi-Hung
authors: BH
authors: Peng
authors: Aida
authors: A
authors: Walker
authors: Jenna
authors: J
authors: Linde
authors: Jennifer
authors: J
authors: Smith
authors: Milagros
authors: M
authors: Salazar
authors: Slobodan
authors: S
authors: Paessler
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001921:Brain / Q000821:virology*; D002493:Central Nervous System Diseases / Q000517:prevention & control / Q000821:virology*; D004195:Disease Models, Animal; D004685:Encephalomyelitis, Venezuelan Equine / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008813:Mice, Inbred ICR; D059906:Neuroimaging / Q000379:methods*; D011070:Poly I-C / Q000494:pharmacology; D011072:Poly U / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D011072:Poly U; C047490:poly(I).poly(c12,U); D011070:Poly I-C