Precision mouse models with expanded tropism for human pathogens
Public Deposited- Creator
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Wahl, Angela
- Affiliation: School of Medicine, Center for AIDS Research
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De, Chandrav
- Affiliation: School of Medicine, Center for AIDS Research
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Fernandez, Maria Abad
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Lenarcic, Erik M.
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Xu, Yinyan
- Affiliation: School of Medicine, Center for AIDS Research
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Cockrell, Adam S.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Cleary, Rachel A.
- Affiliation: School of Medicine, Center for AIDS Research
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Johnson, Claire E.
- Affiliation: School of Medicine, Center for AIDS Research
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Schramm, Nathaniel J.
- Affiliation: School of Medicine, Center for AIDS Research
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Rank, Laura M.
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Newsome, Isabel G.
- Affiliation: School of Medicine, Joint Department of Biomedical Engineering, North Carolina State University
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Vincent, Heather A.
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Sanders, Wes
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Aguilera-Sandoval, Christian R.
- Affiliation: School of Medicine, Center for AIDS Research
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Boone, Allison
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Hildebrand, William H.
- Other Affiliation: University of Oklahoma Health Sciences Institute
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Dayton, Paul A.
- Affiliation: School of Medicine, Joint Department of Biomedical Engineering, North Carolina State University
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Baric, Ralph S.
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Pickles, Raymond J.
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Braunstein, Miriam
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Moorman, Nathaniel J.
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Goonetilleke, Nilu
- Affiliation: School of Medicine, Department of Microbiology and Immunology
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Garcia, J. Victor
- Affiliation: School of Medicine, Center for AIDS Research
- Abstract
- A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics.
- Date of publication
- 2019
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Journal title
- Nature Biotechnology
- Journal volume
- 37
- Journal issue
- 10
- Page start
- 1163
- Page end
- 1173
- Language
- English
- ISSN
- 1087-0156
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