The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 2005-2006

In vivo imaging with biofluorescent virus

Diane E. Griffin, PhD
Johns Hopkins Bloomberg School of Public Health

Animals are essential for the study of how viruses cause paralysis and death due to encephalomyelitis and for determining how such infections can be treated. Traditionally, these pathogenesis and treatment studies involve examining the brains and spinal cords of mice at multiple times after infection to determine where the virus is, how much virus is present and the host immune response to the virus. We have shown that viruses engineered to express bioluminescent molecules such as firefly luciferase can be used to follow virus repliation and spread using only a small number of mice that can be followed individually over time. Emission of light for imaging requires injection of luciferin for each imaging session. In this project we will develop viruses that express a biofluorescent molecule that will emit light on its own without the need for luciferin. This will accomplish 2 goals - (1) quantitation of virus without the need for injection of luciferin and (2) potential expansion of the studies for imaging of both the virus and the host response. Imaging of the host response will use newly engineered mice that have a bioluminescent molecule (e.g. luciferase) that is a reporter for expression of genes that are turned on during inflammation of the brain. Much of the damage during virus infection of the brain is due to the inflammatory response that damages cells in the nervous system. These mice will allow this factor to be monitored without killing the mice and will allow us to determine the effects of treatmenton the inflammatory response.