12/12/2022 0 Comments Scid cured![]() ![]() This model accurately mimics acute HIV-1 infection with rapid CD4 +T-cell loss, with a main benefit being that it can be infected soon after the human cells are injected. HIV-1 infection distorted thymic tissue but did not stop new T-cell generation, with cART preventing new viral replication. cART treatment of these infected hu-SCID mice resulted in renewed thymopoiesis and a normal distribution of T-cell receptor variable gene families ( Table 1). Scid cured full#The model’s susceptibility to HIV-1 infection and replication proved to be of overall benefit for studying HIV-1 infection and the efficacy of antiretroviral therapies or neutralizing antibodies, despite its inability to generate a human immune response due to lack of the full spectrum of immune cells. The first two humanized mouse chimeric hu-SCID models were designed by engrafting the SCID mice 1) with adult human PBLs and 2) with human fetal thymus or liver tissue ( Table 1). These mice do not produce mature CD4 +T and CD8 +T- cells, and therefore were not useful for HIV-1 research but were useful for xenotransplantation studies. Nude mice, first developed in the mid-1960s, carry a mutation in the gene encoding the fork head box protein N1 ( Foxnl nu), which results in abnormal fur growth and an athymic phenotype due to defects in thymic stromal development. In this review, we describe three of the most used mouse models for HIV research. Different technical steps have been used to generate versatile humanized mice, including injection routes, mouse age, irradiation sources, and immunodeficient mouse strains. Therefore, immunodeficient mice engrafted with vital human cells and tissues, i.e., “humanized mice”, have become an increasingly popular and utilized option in a variety of HIV-1 preclinical studies. To overcome these issues, there have been extensive efforts in the last three decades to design functional, humanized immunodeficient mouse models as a tool that can properly mimic HIV-1 infection and pathogenesis in vivo. Moreover, SIV infection is an inexact model for HIV-1 infection. Despite significant contributions of non-human primate models to HIV-1 therapeutic design and vaccine research, these animal models are not fully suitable for in vivo HIV-1 research due to ethical problems and high maintenance costs. In general, there is also a limited availability of human tissues (especially, Central Nervous System ) at various stages of the disease, which have been treated with different regimens, and untreated samples. ![]() ![]() Because of logistical, administrative, and ethical restrictions when working with human donor tissue samples, development of new antiretroviral therapies requires suitable small animal models that accurately mimic the natural course of HIV-1 infection in humans. These humanized mouse models have been tailored in recent decades and heavily employed to address specific quintessential and remaining questions of HIV-1 persistence, pathogenesis and ultimately, eradication.ĭifferent humanized mouse models have been introduced to enable HIV-1 research in vivo, which has been made possible by the development of immunodeficient mouse strains. In this review, we evaluate multiple humanized mouse models while presenting their strengths and limitations for HIV-1 research. The best humanized mouse models would allow a thorough evaluation of antiretroviral strategies that are aimed towards reducing the establishment and size of the HIV-1 reservoirs. An ideal animal model should recapitulate the main aspects of human-specific HIV-1 infection and pathogenesis with their associated immune responses, while permitting invasive antiretroviral studies. Animal models have been a crucial tool in the drug discovery process for investigation of HIV-1 disease mainly in preclinical evaluations of antiretroviral drugs and vaccines. A safe and effective cure strategy for HIV-1 infection will require appropriate animal models that properly mimic HIV-1 infection and advance HIV-1 cure research. A cure for HIV-1 is highly desirable to stop both the spread of the virus in humans and disease progression in HIV-1 patients. However, cART cannot fully clear the virus from the infected patients. Standard combined antiretroviral therapy (cART) has been successfully developed and has given remarkable results suppressing HIV-1 infection and transmission. Despite decades of intensive basic and clinical research efforts, there is still no successful vaccine candidate against human immunodeficiency virus (HIV-1). ![]()
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