Core B: Animal Core

PROJECT SUMMARY/ABSTRACT – CORE B: Animal Models Use and Development Core In this competing renewal P01 application, Core B (Animal Model Core) will support the development and use of the animal models utilized within this Program Project Grant. The guiding principles for the animal model core are efficient planning and utilization of animals, standardization of processing and diagnoses, reliability of service and consistent evaluation of animal models. The fundamental expertise provided within the core is laboratory animal medicine and clinical and anatomic pathology. The specific aims of Core B are: a. Collaboration with Project 1: The antibody response as well as T cell responses of HLA-A2 restricted epitopes will be tested after vaccination with mRNA vaccines in HLA-transgenic mice. The immunogenicity and protective ability of mRNA vaccines will be evaluated in rabbits against infection, and protection against proliferative disease in humanized mice transgenic for HLA-A2. b. Collaboration with Project 2: HTLV-1 infected T cell lines (HTLV+T) will be inoculated into NCG/hIL2 mice with subsequent analysis of HTLV+T by flow cytometry and RNA sequencing. HTLV+T or their extracellular vesicles (sEV) will also be introduced, and their effects on the bone microenvironment assessed morphologically and with single cell RNA sequencing approaches. sEV effects will also be tested with antagonists to sEV-derived miRNAs, and in mice lacking serum amyloid As (SAAs). c. Collaboration with Project 3: Rabbits and HIS mice will be infected with HTLV with mutations in the viral enhancer element (vEnhancer) and vCTCF-BS to study persistent infection or disease development, respectively. NSG mice will be implanted with ATLL cell lines with or without deletion of the vCTCF-BS in order to study its influence on DNA looping and tumor development as well as epigenomic regulation of HTLV reactivation.