A Hitchhiker's guide to humanized mice: new pathways to studying viral infections

Abstract

SummaryHumanized 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.

Haematopoietic stem cell reprogramming and the hope for a universal blood product

“…Increasingly immunocompromised mouse strains on the nonobese diabetic (NOD) genetic background have been developed as a means to improve long-term engraftment of both normal and malignant haematopoietic cells [100][101][102][103]. Increasingly immunocompromised mouse strains on the nonobese diabetic (NOD) genetic background have been developed as a means to improve long-term engraftment of both normal and malignant haematopoietic cells [100][101][102][103].…”

Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research

“…These present a diversity of opportunities for better understanding of human disease conditions as well as a number challenges that also may be informative if approached critically and scientifically. 431,566,567 For a comprehensive overview on this topic, readers are encouraged to consult the contribution from Simons et al in the present issue of the ILAR Journal.…”

Mapping innate and adaptive immune function in arbovirus infections

“…However, the susceptible knockouts are necessarily abnormal in their responses due to the loss of the virus‐induced innate‐adaptive link supplied by the initial interferon activation. Efforts to use mouse models in studies to overcome this conundrum have recently been reviewed . Winkler and Peterson offered a synthesis of the comparative findings from Zika challenge studies of wild‐type and knockout mice .…”

“…Winkler and Peterson offered a synthesis of the comparative findings from Zika challenge studies of wild‐type and knockout mice . An alternative and rapidly emerging area is the use of humanized mice to supply a more pertinent model of the cellular tropisms, immunology and pathology of infection by human pathogens . Skelton and colleagues highlight the value of the plethora of available models for picking apart the fine detail of infection by Zika and other viruses.…”

“…Efforts to use mouse models in studies to overcome this conundrum have recently been reviewed. 13,14 Winkler and Peterson offered a synthesis of the comparative findings from Zika challenge studies of wild-type and knockout mice. 13 An alternative and rapidly emerging area is the use of humanized mice to supply a more pertinent model of the cellular tropisms, immunology and pathology of infection by human pathogens.…”