Abstract
The development of safe and effective combination antiretroviral therapies for human immunodeficiency virus (HIV) infection over the past several decades has significantly reduced HIV-associated morbidity and mortality. Additionally, antiretroviral drugs have provided an effective means of protection against HIV transmission. Despite these advances, significant limitations exist; namely, the inability to eliminate HIV reservoirs, the inability to reverse lymphoid tissues damage, and the lack of an effective vaccine for preventing HIV transmission. Evaluation of the safety and efficacy of therapeutics and vaccines for eliminating HIV reservoirs and preventing HIV transmission requires robust in vivo models. Since HIV is a human-specific pathogen, that targets hematopoietic lineage cells and lymphoid tissues, in vivo animal models for HIV-host interactions require incorporation of human hematopoietic lineage cells and lymphoid tissues. In this review, we will discuss the construction of mouse models with human lymphoid tissues and/or hematopoietic lineage cells, termed, human immune system (HIS)-humanized mice. These HIS-humanized mouse models can support the development of functional human innate and adaptive immune cells, along with primary (thymus) and secondary (spleen) lymphoid tissues. We will discuss applications of HIS-humanized mouse models in evaluating the safety and efficacy of therapeutics against HIV reservoirs and associated immunopathology, and delineate the human immune response elicited by candidate HIV vaccines. In addition to focusing on how these HIS-humanized mouse models have already furthered our understanding of HIV and contributed to HIV therapeutics development, we discuss how emerging HIS-humanized rat models could address the limitations of HIS-mouse models.
Highlights
Despite combination antiretroviral therapymediated suppression of human immunodeficiency virus (HIV) replication and promotion of immune reconstitution in patients, HIV-associated morbidity persists and is associated with the latent reservoir, unresolved immune abnormalities, and fibrosis in lymphoid organs [1].Agarwal et al Retrovirology (2020) 17:8HIV transmission remains endemic across the globe, and development of a functional cure and/or an effective vaccine will be required to end this epidemic [2]
Despite successful prevention of HIV transmission with antiviral drugs, it is likely that an effective vaccine provides the only means of ending the HIV epidemic [2]
CART has significantly reduced the morbidity and mortality associated with chronic HIV infection, the HIV reservoir persists in people living with HIV (PLHIV) and is associated with chronic inflammation, lymphoid tissue damage, and a myriad of end-organ diseases [1]
Summary
Despite combination antiretroviral therapy (cART)mediated suppression of human immunodeficiency virus (HIV) replication and promotion of immune reconstitution in patients, HIV-associated morbidity persists and is associated with the latent reservoir, unresolved immune abnormalities, and fibrosis in lymphoid organs [1].Agarwal et al Retrovirology (2020) 17:8HIV transmission remains endemic across the globe, and development of a functional cure and/or an effective vaccine will be required to end this epidemic [2]. HIV is a human specific pathogen; animal models for evaluating the safety and efficacy of therapeutics and vaccines directly against HIV requires the incorporation of human lymphoid tissues and/or hematopoietic lineage cells.
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