Imaging of CNS Invasion by Venezuelan Equine Encephalitis Virus

Principal Investigator: Slobodan Paessler, DVM/PhD

With dozens of emerging and reemerging viruses currently recognized around the globe, the need for vaccines or therapeutics has never been more important for both developing and developed countries. Advancing technologies such as In Vivo Imaging Systems (IVIS) are key tools for a new methodology of studying these pathogens. The development of an IVIS murine encephalitic model will assist not only in studying disease progression but also in identifying novel antivirals and vaccines. The capability to collect multiple data points from a single animal without the need for sacrifice insures IVIS modeling reduces research time, animal numbers, and animal morbidity while increasing accuracy of detecting virus progression and safety for researchers.

The study of Venezuelan Equine Encephalitis virus (VEEV) invasion of the CNS is an ideal system to utilize IVIS and develop a standardized model. VEEV is a reemerging zoonotic virus about which very little is known of the progression of the disease leading to encephalitis and neurological sequelae. VEEV is an ideal virus to develop an IVIS modeling system both due to the ease of inserting a transgenetic bioluminescent gene into the viral genome and how much is already known of the mechanisms of viral pathogenesis. There is no FDA approved human vaccine or therapeutic providing the opportunity to utilize an IVIS model to identify efficacy of untested drugs.

Our first aim is to develop a standardized modeling system for tracking CNS infection following intranasal challenge. The second aim is to utilize this model to track protection against VEEV with CNS invasion being the endpoint of the study. Protection regiments will include the IND vaccine strain TC83 and the TLR3 agonist Ampligen. As an innate immune stimulator and interferon inducer, Ampligen is a potential non-specific therapeutic for many viral infections. Standardization of this modeling system for VEEV can be translated to other viruses found worldwide known to cause neural sequelae and death, decreasing costs and decreasing research time by assisting with screening of new anti-virals and vaccines.