Precision mouse models with expanded tropism for human pathogens.

Autor: Wahl A; Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA. angela_wahl@med.unc.edu., De C; Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA., Abad Fernandez M; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA., Lenarcic EM; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA., Xu Y; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA., Cockrell AS; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA., Cleary RA; Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA., Johnson CE; Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA., Schramm NJ; Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA., Rank LM; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA., Newsome IG; Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, NC, USA., Vincent HA; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA., Sanders W; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA., Aguilera-Sandoval CR; Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA.; BD Life Sciences, San Jose, CA, USA., Boone A; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.; Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA., Hildebrand WH; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Dayton PA; Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, NC, USA., Baric RS; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA., Pickles RJ; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.; Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA., Braunstein M; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA., Moorman NJ; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA., Goonetilleke N; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.; UNC HIV Cure Center, University of North Carolina, Chapel Hill, NC, USA., Victor Garcia J; Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA. victor_garcia@med.unc.edu.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2019 Oct; Vol. 37 (10), pp. 1163-1173. Date of Electronic Publication: 2019 Aug 26.
DOI: 10.1038/s41587-019-0225-9
Abstrakt: 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.
Databáze: MEDLINE
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