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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.
Highlights
Infectious diseases caused by human pathogenic viruses remain a huge threat to global health.An estimated 37 million persons are living with human immunodeficiency virus (HIV) infections [1].More than 90 million new cases of influenza occur every year in children aged less than five years; of these, 20 million are acute lower respiratory infections and one million are severe acute lower respiratory tract infection (ALRI) cases [2]
An ideal animal model for human viral disease should closely recapitulate the spectrum of clinical symptoms and pathogenesis seen during the course of human infection
This rule suits conditions where vaccines and therapeutics cannot be tested safely or ethically on humans; in these cases, approval is possible only after preclinical tests are conducted on animal models
Summary
Infectious diseases caused by human pathogenic viruses remain a huge threat to global health. These transgenic mice include mice expressing a transgenic TCR specific to influenza virus hemagglutinin (HA) in the context of the major histocompatibility complex (MHC) class II molecules These mice, when infected with mouse adapted strains of influenza, show both a CD4+ and CD8+ T cell response, and have been used to study the role of CD4+ T cells in the activation of CD8+T cells [4,5]. Many human viruses like hepatitis viruses, polioviruses, papillomaviruses, HIV, and measles are not infectious to wild-type mice, but the transgenic mice expressing specific human receptors that aid in the entry of those viruses are susceptible to many of these viruses These susceptible Tg mice can be used to evaluate the virus’ pathogenesis as in vivo models [6]. Knockout (KO) mice devoid of specific genes have been used to identify and evaluate the cellular and molecular entities involved in the adaptive and innate immune responses that are important in controlling viral infections.
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