Abstract
Immunodeficient mice engrafted with human tissues provide a robust model for the in vivo investigation of human-restricted viruses such as human cytomegalovirus (HCMV). Several humanized mouse models have been developed and improved over the last 30 years. Here, we describe a protocol for the transplant of human hematopoietic stem cells with autologous fetal liver and thymic tissues into NOD.Cg-PrkdcscidIL2rγtm1Wjl mice to create a humanized bone marrow–liver–thymus model (huBLT) that can be infected with HCMV. The presence of human thymus allows the development of a functional human immune system, including HLA-restricted human T-cells and B-cells. Indeed, following infection, huBLT mice generate virus-specific CD4+ and CD8+ T-cell responses. Additionally, both HCMV-specific IgM and IgG B-cell responses can be detected. This huBLT model provides the first animal model to explore the adaptive human immune response to HCMV infection.
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Acknowledgments
We would like to thank L. Drew Martin, DVM, DACLAM for veterinary oversight in setting up these protocols; and Christopher Parkins, Andrew Pham, and Rebecca Tempel, PhD for technical assistance on various cohorts of huBLT mice. This work was supported by NIH funding P01 AI127335.
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Crawford, L.B., Caposio, P. (2021). Development of a huBLT Mouse Model to Study HCMV Latency, Reactivation, and Immune Response. In: Yurochko, A.D. (eds) Human Cytomegaloviruses. Methods in Molecular Biology, vol 2244. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1111-1_17
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DOI: https://doi.org/10.1007/978-1-0716-1111-1_17
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