GENE DISCOVERY IN PLAGUE, BRUCELLOSIS AND TULAREMIA; HOST-PATHOGEN INTERACTIONS AND IMMUNE RESPONSE IN CHRONIC WASTING DISEASE

(WYO-00599)

Project A: Plague and brucellosis represent re-emerging zoonotic diseases in numerous animal species, domestic and wild, in the Western U.S. Although the pathology of these infections has been well studied, the molecular mechanisms by which their associated bacterial agents cause disease remain enigmatic. Bacterial genes up-regulated during infection may encode proteins useful as protective components for vaccines or as diagnostic targets for bacterial animal disease agents. Our research to date, based on the application of in vivo-induced antigen technology (IVIAT) on Yersinia pestis, the bacterium which causes plague and Brucella abortus, the agent of brucellosis in domestic livestock and wild animals, has resulted in the identification of over 30 genes expressed during infection by these disease agents. Furthermore, we have found almost all these genes to encode proteins highly conserved through the course of evolution. To support our hypothesis that these gene products represent a common theme associated with pathogenic processes in different diseases, we will further study these proteins in our laboratory (in vitro and in vivo), in addition to characterizing the common gene products of B. abortus, Y. pestis, and Francisella tularensis (the agent of tularemia) identified through gene homology searches using our existing IVIAT data. We also intend to conduct similar studies on F. tularensis to identify and characterize genes up-regulated during infection using our previously employed gene discovery methodology. Project B: Prion replication in scrapie of sheep and goats and chronic wasting disease (CWD) of deer and elk occurs throughout lymphoid tissue before neuroinvasion and the ensuing fatal neurodegenerative disease. To understand the role of follicular dendritic cells (FDC) of tonsils and lymph nodes in early infection of natural hosts such as mule deer and elk with CWD, we will determine phenotypes of lymphoid follicle cells expressing cellular PrP (PrPC) in deer and elk, develop a cervid-specific monoclonal antibody recognizing FDCs, test both PrPC and infectious prion (PrPSc) for attachment to follicle cells by GPI anchor using PIPLC digestion, and explore the feasibility of developing a binding assay for soluble complement protein C1q and PrPSc.

USDA CRIS Project Information Link: 0214478