A Hitchhiker's guide to humanized mice: new pathways to studying viral infections
Open Access
- 15 February 2018
- journal article
- review article
- Published by Wiley in Immunology
- Vol. 154 (1) , 50-61
Abstract
Summary: Humanized mice are increasingly appreciated as an incredibly powerful platform for infectious disease research. The often very narrow species tropism of many viral infections, coupled with the sometimes misleading results from preclinical studies in animal models further emphasize the need for more predictive model systems based on human cells rather than surrogates. Humanized mice represent such a model and have been greatly enhanced with regards to their immune system reconstitution as well as immune functionality in the past years, resulting in their recommendation as a preclinical model by the US Food and Drug Administration. This review aims to give a detailed summary of the generation of human peripheral blood lymphocyte‐, CD34+ haematopoietic stem cell‐ and bone marrow/liver/thymus‐reconstituted mice and available improved models (e.g. myeloid‐ or T‐cell‐only mice, MISTRG, NSG‐SGM3). Additionally, we summarize human‐tropic viral infections, for which humanized mice offer a novel approach for the study of disease pathogenesis as well as future perspectives for their use in biomedical, drug and vaccine research.Keywords
Funding Information
- H2020 European Research Council (ERC-StG-2015-637304)
- Wellcome Trust (104771/Z/14/Z)
This publication has 99 references indexed in Scilit:
- Cryptopatches Are Essential for the Development of Human GALTCell Reports, 2013
- Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV-1 envelope proteins are largely mediated via human CD5+ B cellsImmunology, 2011
- One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used According to the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection, Validating the BLT Model for Evaluation of New Microbicide CandidatesJournal of Virology, 2011
- Transgenic expression of human signal regulatory protein alpha in Rag2−/−γc−/−mice improves engraftment of human hematopoietic cells in humanized miceProceedings of the National Academy of Sciences, 2011
- The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized miceJournal of Experimental Medicine, 2011
- Immune reconstitution of the female reproductive tract of humanized BLT mice and their susceptibility to human immunodeficiency virus infectionJournal of Reproductive Immunology, 2011
- Granulocyte-Colony Stimulating Factor Reactivates Human Cytomegalovirus in a Latently Infected Humanized Mouse ModelCell Host & Microbe, 2010
- Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2rγnullhumanized miceProceedings of the National Academy of Sciences, 2010
- Priming of protective T cell responses against virus-induced tumors in mice with human immune system componentsJournal of Experimental Medicine, 2009
- Mucosal transmission of R5 and X4 tropic HIV-1 via vaginal and rectal routes in humanized Rag2−/−γc−/− (RAG-hu) miceVirology, 2008