April 1, 2020
Many challenging viral diseases, such as viral hepatitis, AIDS, Dengue fever or yellow fever are caused by viruses that display a very narrow host tropism often restricted to human. For this reason, studying the biology of human-tropic viruses in vivo, andunderstanding how they interact with human components over time and space, has remained a challenging endeavor. Humanized mice, i.e. mice engrafted with human tissues, have emerged as powerful tools for studying the infectious cycle of a broad range of human(-tropic) pathogens in vivo. Recent improvements in engraftment protocols and genetic engineering have opened unprecedented opportunities for the generation of more advanced humanized mouse systems able to recapitulate more faithfully human biological processes, such human immune responses against viral pathogens. Our laboratory aims at using and developing advanced humanized mouse models to identify and characterize fundamental human immunological mechanisms and human-virus interactions that govern viral pathogenicity and immunogenicity during virus infection. Altogether, we envision that our work could pave the toward novel vaccine and immunotherapy strategies against challenging infectious diseases.Here, I will present some of the most recent humanized mouse systems we have been developing to investigate the infectious cycle and immunogenicity of a flavivirus, yellow fever virus. I will discuss the potential of these new models for investigating other pathogens, and describe our efforts to continuously refine them. Finally, I will introduce alternative models for which tolerance to virus infection solely relies on genetic humanization.