Development and Characterization of a Sublethal-Sequelae Mouse Model of EEEV Infection
Abstract
We have seen the rapid, worldwide spread of mosquito-transmitted viruses as a consequence of globalization. Mosquito-borne viruses, referred to as arboviruses, are of concern because many of these are known to cause severe acute human disease, there are few effective vaccines and therapeutics against them, and many of these viruses have been previously weaponized. Encephalitic arboviruses such as eastern, Venezuelan, and western equine encephalitis viruses (EEEV, VEEV and WEEV, respectively) cause disease in both horses and humans, with infection resulting in high patient death rates, as well as neurological damage in those patients that survive. The current natural range of EEEV encompasses North, Central, and South America. It is also associated with a very high mortality rate (50%-78% of infected patients) relative to other encephalitic arboviruses, as well as a high incidence of neurological damage in surviving patients. Unfortunately, no vaccines or therapeutics are available that are effective against EEEV, and their development is hampered by the lack of essential well-characterized animal models for the disease. Such animal models are a critical tool to the drug development process because these drugs must be approved by testing in animal models. We propose to perform a comprehensive analysis of the host response in mice to EEEV infection. Our studies will be the first to systematically dissect the ability of EEEV to cause disease (pathogenesis) and the associated host responses at the molecular level. We also propose to study the neurological damage that can be inflicted by EEEV in our mouse model with the same molecular rigor in our analyses. The data generated will be used to identify potential pathways that can be targeted by therapeutics to prevent neurological disease. These studies will lay the foundation for developing models to study neurological damage observed following other arboviral infections, including VEEV, WEEV, chikungunya virus, and West Nile virus. While the immediate beneficiaries of this research would be members of the military who currently work with or may come into contact with EEEV, ultimately the global civilian population would also benefit from the fruits of the proposed research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210357
Entities
People
- Kylene Kehn-Hall
Organizations
- United States Army
- Virginia Tech