Entry of alaphaviruses to the macaque brain and viral persistence: correlation with development of encephalitis
Abstract
VEEV, and EEEV are members of the Togaviridae family of positive-sense RNA alphaviruses, and cycle in nature between mosquitoes and birds (EEEV), mosquitoes and rodents (VEEV enzootic cycle), or mosquitoes and horses (VEEV epizootic cycle). Together, VEEV and EEEV are widely distributed in North, Central, and South America. Human infection can progress rapidly to encephalitis with fatality rates of ~1% in VEEV symptomatic cases and remarkably, 30 to 70% in EEEV symptomatic cases. Although the number of human cases reported is small, the possibility for disease emergence is high due to expansion and spread of mosquito vectors. Moreover, there is the potential for even moderately experienced scientists to grow VEEV and/or EEEV to high-titer and generate aerosol forms, which could cause severe disease in a dense urban or military population. Despite the documented epidemic potential of VEEV and the high morbidity and case fatality rate of EEEV, there are no approved vaccines or therapeutics for humans. The objective of the current proposal is to continue and refine previous natural history studies of VEEV and EEEV in the macaque model, which is well positioned to satisfy the FDA Animal Rule or approval of antiviral drugs and vaccines.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 19, 2022
- Source ID
- HDTRA12210030
Entities
People
- William B Klimstra
Organizations
- Defense Threat Reduction Agency
- University of Pittsburgh