Humanized Mouse Models for Human Immunodeficiency Virus Infection

Abstract

Human immunodeficiency virus (HIV) remains a significant source of morbidity and mortality worldwide. No effective vaccine is available to prevent HIV transmission, and although antiretroviral therapy can prevent disease progression, it does not cure HIV infection. Substantial effort is therefore currently directed toward basic research on HIV pathogenesis and persistence and developing methods to stop the spread of the HIV epidemic and cure those individuals already infected with HIV. Humanized mice are versatile tools for the study of HIV and its interaction with the human immune system. These models generally consist of immunodeficient mice transplanted with human cells or reconstituted with a near-complete human immune system. Here, we describe the major humanized mouse models currently in use, and some recent advances that have been made in HIV research/therapeutics using these models.

Lentiviral Vector-Based Dendritic Cell Vaccine Suppresses HIV Replication in Humanized Mice

“…To test the ability of transduced DCs to induce an anti-HIV-1 T cell response and to suppress HIV-1 replication in vivo, we used the humanized BLT mouse model in which non-obese diabetic-severe combined immunodeficiency (NOD-SCID)-common g-chain knockout mice are transplanted with human fetal liver, thymus, and bone marrow tissue to reconstitute a functional human immune system. 39,40 The mice support HIV replication and mount CD4 and CD8 T cell responses. Upon infection, plasma virus loads rapidly rise to a set point after which the peripheral blood and lymphoid organ CD4 T cells are gradually depleted.…”

Human Interleukin-34 facilitates microglia-like cell differentiation and persistent HIV-1 infection in humanized mice

“…Without such cells the ability to represent viral restriction and latency in the nervous system during cART is limited. Humanized mice developed by reconstituting immune compromised mice with human hematolymphoid system have been important tools to study hematopoiesis, cancer, autoimmunity, infections and degenerative disorders [4][5][6]. Previously we used humanized mice transplanted with human hematopietic stem cells (HSPC) in NOD/ Scid IL2Rγ−/− (NSG/NOG) mice to study HIV persistence in brain and its associated neurodegenration [7][8][9][10].…”

Mouse Models as Resources for Studying Infectious Diseases

“…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. 59,61 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.…”

“…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. Human liver xenograft mice have been shown to support replication of hepatitis viruses B, C, D, and E, and these models are useful for studying the pathogenesis of virus-induced liver injury, and as platforms for evaluating potential therapies to treat acute and chronic HCV and hepatitis B virus infection.…”