The use of humanized mice for studies of viral pathogenesis and immunity

Abstract

Humanized mice, that is, animals engrafted with human tissues and/or expressing human genes, have been instrumental in improving our understanding of the pathogenesis and immunological processes that define some of the most challenging human-tropic viruses. In particular, mice engrafted with components of a human immune system (HIS) offer unprecedented opportunities for mechanistic studies of human immune responses to infection. Here, we provide a brief overview of the current panel of HIS mouse models available and cite recent examples of how such humanized animals have been used to study immune responses and pathogenesis elicited by human-tropic viruses. Finally, we will outline some of the challenges that lay ahead and strategies to improve and refine humanized mice with the goal of more accurately recapitulating human immune responses to viral infection.

Figure 1. Current and future humanized mouse models for the study of viral infection and immunity

Advantages (green text) and limitations (red text) of conventional HIS mice and second-generation HIS mice (myeloid-improved HIS mice and human-microenvironment HIS mice) are shown. Across the entire figure, humanization levels are symbolized by a color gradient from white (unaltered/wildtype mice) to red (humans). Examples of viral pathogens are listed in a box beside the respective model in which they have been studied. Pictograms representing the specific characteristics and/or improvements of each category are shown (legend at bottom of figure). Characteristics/improvements not ubiquitously present across all HIS mice models of a given category (conventional or second-generation) are indicated in parentheses. Putative improvements of second-generation HIS mice toward the generation of third-generation HIS mice are depicted in yellow circles. HSC, human hematopoietic cells.