Abstract
Immunodeficient mice transplanted with human cell populations or tissues, also known as human immune system (HIS) mice, have emerged as an important and versatile tool for the in vivo study of human immunodeficiency virus-type 1 (HIV-1) pathogenesis, treatment, and persistence in various biological compartments. Recent work in HIS mice has demonstrated their ability to recapitulate critical aspects of human immune responses to HIV-1 infection, and such studies have informed our knowledge of HIV-1 persistence and latency in the context of combination antiretroviral therapy. The central nervous system (CNS) is a unique, immunologically privileged compartment susceptible to HIV-1 infection, replication, and immune-mediated damage. The unique, neural, and glia-rich cellular composition of this compartment, as well as the important role of infiltrating cells of the myeloid lineage in HIV-1 seeding and replication makes its study of paramount importance, particularly in the context of HIV-1 cure research. Current work on the replication and persistence of HIV-1 in the CNS, as well as cells of the myeloid lineage thought to be important in HIV-1 infection of this compartment, has been aided by the expanded use of these HIS mouse models. In this review, we describe the major HIS mouse models currently in use for the study of HIV-1 neuropathogenesis, recent insights from the field, limitations of the available models, and promising advances in HIS mouse model development.
Highlights
Infection with human immunodeficiency virus-type 1 (HIV-1) results in CD4+ T cell destruction and progressive debilitation of the immune system [1]
Resulting central nervous system (CNS) immune activation; the infection and activation of monocytes, perivascular macrophages, and resident microglia; and indirect mechanisms are all thought to play a critical role in the pathogenesis of HIV-1 in the CNS [12,13,14,15,16]
The ability of these strains to support long-term, systemic reconstitution with human cells were, limited by relatively high residual levels of innate immune responses, such as those mediated by natural killer (NK) cells resulting in the rejection of human bonemarrow allographs [46]
Summary
Infection with human immunodeficiency virus-type 1 (HIV-1) results in CD4+ T cell destruction and progressive debilitation of the immune system [1]. Immunodeficient mice used for human tissue or cell xenografts included “nude” mice, which lack mature CD4+ and CD8+ T cells [44] and severe combined immunodeficiency (SCID) mice, which harbor a mutation in the protein kinase, DNA-activated, catalytic polypeptide gene (Prkdcscid) and lack mature T and B cells [45] The ability of these strains to support long-term, systemic reconstitution with human cells were, limited by relatively high residual levels of innate immune responses, such as those mediated by natural killer (NK) cells resulting in the rejection of human bonemarrow allographs [46].
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