Eastern, Venezuelan, and Western equine encephalitis (EEE, VEE, WEE) viruses (Alphavirus;Togaviridae) are mosquito-borne viruses causing severe encephalitis in humans and horses. All threeviruses are listed as category B agents by both NIAID and CDC and as potential bioterrorism/biowarfare(BT/BW) agents. There are enormous knowledge gaps concerning transmission potential, mosquito-hostdeterminants, pathogenesis from aerosolized virus, acquired and innate immune responses, etc. for thisgroup of viruses, especially EEEV and WEEV. In this project, we will develop alphavirus (EEEV and WEEV)infectious cDNA clones to determine molecular mechanisms of viral replication and pathogenesis in miceand infectivity of mosquitoes that may serve as vectors in secondary transmission during a BT/BW event.We will also develop stable, double subgenomic EEEV, VEEV, and WEEV transducing viruses tocharacterize their ability to replicate and express a reporter gene in infected mice and vectors. We will alsoconduct pathogenesis studies focusing primarily on EEEV and WEEV in small animal models, but will alsoinclude transducing viruses from the three alphaviruses in these studies. We will focus on pathogenesis inmice following infection by vector and aerosol routes of infection. Finally we will characterize virus-vectorinteractions for all three viruses that may lead to increased transmission potential by vectors of BT/BWagents and emerging alphavirus pathogens.Project Interactions: The Pi's of the project are Drs. Ann M. Powers and Ken E. Olson. Drs. Powers andOlson are located at the Centers for Disease Control, Division of Vector-borne Infectious Diseases andArthropod-borne Infectious Diseases Laboratory (CSU) in Fort Collins, Co., respectively. Dr. Powers andOlson both have considerable experience in alphavirus biology, molecular biology, vector biology and aredeveloping expertise in alphavirus interactions with small animal models. In addition, the project will interactwith other investigators in the RCE. Specifically, with Drs. Kedl, Blair, and Dow on Lanacs studies (II.C.6),Drs. Titus and Beaty (II.B.2.) and Dr. Chang (II.B.3) on novel vaccine technologies, Dr. Morrey (II.G) insharing infectious alphavirus clones and transducing viruses developed in this project and Dr. Fujinami andFoy (II.H.2) on RNAi-based antiviral therapies. This project will be a resource for developing protocols,viruses, and reagents that can be used by other members of the RCE. Finally, this project will be dependenton two SFC's: Animal Models Core (III.A) and Genomics/Proteomics Core (III.C).
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