Precision mouse models with expanded tropism for human pathogens

被引:0
作者
Angela Wahl
Chandrav De
Maria Abad Fernandez
Erik M. Lenarcic
Yinyan Xu
Adam S. Cockrell
Rachel A. Cleary
Claire E. Johnson
Nathaniel J. Schramm
Laura M. Rank
Isabel G. Newsome
Heather A. Vincent
Wes Sanders
Christian R. Aguilera-Sandoval
Allison Boone
William H. Hildebrand
Paul A. Dayton
Ralph S. Baric
Raymond J. Pickles
Miriam Braunstein
Nathaniel J. Moorman
Nilu Goonetilleke
J. Victor Garcia
机构
[1] International Center for the Advancement of Translational Science,Division of Infectious Diseases
[2] Center for AIDS Research,Department of Microbiology and Immunology
[3] University of North Carolina,Department of Epidemiology
[4] School of Medicine,Joint Department of Biomedical Engineering
[5] University of North Carolina,Department of Microbiology and Immunology
[6] Lineberger Comprehensive Cancer Center,undefined
[7] University of North Carolina,undefined
[8] University of North Carolina,undefined
[9] University of North Carolina and North Carolina State University,undefined
[10] Marsico Lung Institute,undefined
[11] University of North Carolina,undefined
[12] University of Oklahoma Health Sciences Center,undefined
[13] UNC HIV Cure Center,undefined
[14] University of North Carolina,undefined
[15] BD Life Sciences,undefined
来源
Nature Biotechnology | 2019年 / 37卷
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摘要
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.
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页码:1163 / 1173
页数:10
相关论文
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