Recent Updates on Mouse Models for Human Immunodeficiency, Influenza, and Dengue Viral Infections

Abstract

Well-developed mouse models are important for understanding the pathogenesis and progression of immunological response to viral infections in humans. Moreover, to test vaccines, anti-viral drugs and therapeutic agents, mouse models are fundamental for preclinical investigations. Human viruses, however, seldom infect mice due to differences in the cellular receptors used by the viruses for entry, as well as in the innate immune responses in mice and humans. In other words, a species barrier exists when using mouse models for investigating human viral infections. Developing transgenic (Tg) mice models expressing the human genes coding for viral entry receptors and knock-out (KO) mice models devoid of components involved in the innate immune response have, to some extent, overcome this barrier. Humanized mouse models are a third approach, developed by engrafting functional human cells and tissues into immunodeficient mice. They are becoming indispensable for analyzing human viral diseases since they nearly recapitulate the human disease. These mouse models also serve to test the efficacy of vaccines and antiviral agents. This review provides an update on the Tg, KO, and humanized mouse models that are used in studies investigating the pathogenesis of three important human-specific viruses, namely human immunodeficiency (HIV) virus 1, influenza, and dengue.

Humanized Mice in Dengue Research: A Comparison with Other Mouse Models

“…In contrast, IFNα/βR −/− Tg C57BL/6J mice develop viremia and disease, recovering and clearing the virus after 6 days [52]. Approximately, 42 T-cell epitopes present in human PBMCs has been identified [87] and by using IFNα/βR −/− Tg and C57BL/6J wild type mice, of 12 epitopes derived from 6 of the 10 DENV proteins were reported [52]. In addition, C57BL/6J Tg expressing human MHC alleles such as HLA, A*0201, A*0101, A*1101, B*0701, and DRB1*0101 have been developed to study T cells in the context of viral infections [87][88][89] opening the possibility of using C57BL/6J-MHC Tg or IFNα/βR −/− -MHC Tg to identify T-cell epitopes relevant to protection against dengue.…”

Mouse Models as Resources for Studying Infectious Diseases

“…59,60 Furthermore, because immune cells and other tissues from the same individual can be used to generate cohorts of humanized mice, it is possible to test responses in sets of individuals carrying tissues from the same genetic background. 61 Although a detailed description of the different types of humanized mouse models, and the methods used in their development is beyond the scope of the present review, we refer the reader to several recent reviews that nicely summarize the current state of xenograft mouse development. 59,62 Mice with xenografted human immune systems have been used to study the pathogenesis of a wide range of infectious agents, including Plasmodium falciparum (malaria), Mycobacterium tuberculosis, dengue virus, and influenza virus.…”

“…59,62 Mice with xenografted human immune systems have been used to study the pathogenesis of a wide range of infectious agents, including Plasmodium falciparum (malaria), Mycobacterium tuberculosis, dengue virus, and influenza virus. 59,61 These models have been particularly useful for studying HIV, including analysis of viral and host factors that promote viral replication, HIV interactions with the host immune response, and as platforms for testing therapeutic approaches for controlling or curing HIV infection. 62 Although the majority of studies using xenografted mice have focused on human immune cells, these models can also be used to evaluate pathogen interactions with solid organs.…”

μ-Lat: A Mouse Model to Evaluate Human Immunodeficiency Virus Eradication Strategies

“…Mouse models represent another alternative with lower costs, more convenient husbandry requirements, as well as greater scalability. In the context of HIV studies, a wide range of small animal models have been developed comprising knockout mouse (16)(17)(18), transgenic mouse (19)(20)(21)(22)(23), and humanized mouse models (6,(24)(25)(26)(27)(28)(29). Humanized mice are established by…”