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 2008-2009

In vivo imaging with biofluorescent viruses

Diane Griffin and Ivorlyne Greene
Johns Hopkins Bloomberg School of Public Health

Animals are essential for the study of how viruses, such as alphaviruses, that infect the nervous system cause paralysis and death and for determining how such infections can be treated to prevent death and longterm sequelae of infection (e.g. paralysis, mental retardation, etc).  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 replication and spread using only a small number of mice that can be followed individually over time.  Recently, we have also shown that mice that express luciferase in a way that reflects the inflammatory response in the nervous system can be used to follow the host response to viral infection, again using only a small number of mice that can be followed individually over time.  These studies also showed that the effects of treatment could be monitored as well.

In this project we will combine the use of bioluminescent viruses and mice expressing host genes as bioluminescent proteins to examine the course of virus infection of the nervous system and the response to various treatments designed to improve the outcome from this type of potentially devastating infection.  The innovative techniques employed will generate this important information with a very small number of mice compared to typical pathogenesis studies.