Due to outstanding progress and important developments in the field of chimeric mouse models reconstituted with human immune systems and cells, Core H, the Small Animal Biocontainment (ABC) Core expanded its scope and now includes two sites. Site A is located at the Massachusetts General Hospital (MGH), and Site B is the existing BL-3 ABC Facility at the Dana-Farber Cancer Institute (DFCI). Site A will provide the following services: 1. Generation of humanized BLT mice (NOD-SCID-Hu mice transplanted wit human fetal thymus, liver and hematopoietic stems cells (HSC)) for CFAR investigators to use for experiments, to be performed at the MGH or DFCI Sites of this core, or at the site of the collaborating investigator, following transfer of the BLT mice to his/her animal facility. 2. Bleeding and flow cytometry of peripheral blood leukocytes of the BLT mice to characterize their human immune reconstitution prior to use by collaborating investigators. 3. For collaborating investigators choosing to perform their experiments at the MGH site, support in the handling and analysis of HIV-infected mice. 4. For collaborating investigators choosing to perform experiments in their own animal facilities, training in the safe handling of HIV-infected mice. 5. Further characterization of the human virus-specific cellular and humoral immune responses generated in HIV-infected BLT mice, to expand the areas of investigation this model can support. Site B will provide the following services: 1. The use of an animal facility in which the spread of contagious agents is prevented between animals. 2. Technical support in handling animals potentially infectious to humans or animals. 3. Access to technical support for performing HIV-1 inoculations into chimeric BLT or NOG (i.e., NOD/SCID.IL-2RYNull) mice reconstituted with CD34+ human HSC, which will be housed to evaluate candidate antiviral agents for efficacy and toxicity in these novel small animal models. A special plus of Site B is the ability to permit work with Mycobacterium tuberculosis (MTb) or HIV-1/MTb co-infections. 4. The use of safe working conditions. 5. Training for safe handling of potential human pathogens in small animal models.
Core H will allow CFAR investigators to study HIV immunopathogenesis and host-virus dynamics in small animal models, which can also support coinfection with HIV-1 and Mycobacterium tuberculosis, two pathogens that threaten public health worldwide.
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