Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy

Terahara, Kazutaka; Iwabuchi, Ryutaro; Tsunetsugu-Yokota, Yasuko

doi:10.3390/v13050776

Cited by 11 publications

(7 citation statements)

References 181 publications

(295 reference statements)

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“…Thus, these alterations should result in improvements in humanization-in particular, higher engraftment levels, better functionality of immune cells, and a better lymphoid architecture. Terahara et al refer to these hu mouse models as "next-generation mouse models" [7].…”

Section: What Are the Attributes Of A Good Hiv Mouse Model?mentioning

confidence: 99%

“…The review does not offer a structured overview of the existing humanized mouse models with their advantages or disadvantages or a comparison of different humanized mouse models independent of HIV; we refer the reader to recently published reviews on this topic [4][5][6][7]. Furthermore, we do not cover the work on the original hu-PBL-SCID and SCID-hu Thy/Liv mice.…”

Section: Introductionmentioning

confidence: 99%

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The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?

et al. 2023

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In the early 2000s, novel humanized mouse models based on the transplantation of human hematopoietic stem and progenitor cells (HSPCs) into immunocompromised mice were introduced (hu mice). The human HSPCs gave rise to a lymphoid system of human origin. The HIV research community has greatly benefitted from these hu mice. Since human immunodeficiency virus (HIV) type 1 infection results in a high-titer disseminated HIV infection, hu mice have been of great value for all types of HIV research from pathogenesis to novel therapies. Since the first description of this new generation of hu mice, great efforts have been expended to improve humanization by creating other immunodeficient mouse models or supplementing mice with human transgenes to improve human engraftment. Many labs have their own customized hu mouse models, making comparisons quite difficult. Here, we discuss the different hu mouse models in the context of specific research questions in order to define which characteristics should be considered when determining which hu mouse model is appropriate for the question posed. We strongly believe that researchers must first define their research question and then determine whether a hu mouse model exists, allowing the research question to be studied.

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Section: What Are the Attributes Of A Good Hiv Mouse Model?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?

et al. 2023

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“…One critical limitation of studies involving humanized mice models is the small size of the mice requiring, in general, pooling of several animals to achieve enough sensitivity to quantify viral reservoirs. The different types of humanized mouse models used to study HIV persistence and their benefits and limitations have been recently reviewed and are only briefly described here [117][118][119].…”

Section: Humanized Micementioning

confidence: 99%

HIV Latency in Myeloid Cells: Challenges for a Cure

et al. 2022

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The use of antiretroviral therapy (ART) for Human Immunodeficiency Virus (HIV) treatment has been highly successful in controlling plasma viremia to undetectable levels. However, a complete cure for HIV is hindered by the presence of replication-competent HIV, integrated in the host genome, that can persist long term in a resting state called viral latency. Resting memory CD4+ T cells are considered the biggest reservoir of persistent HIV infection and are often studied exclusively as the main target for an HIV cure. However, other cell types, such as circulating monocytes and tissue-resident macrophages, can harbor integrated, replication-competent HIV. To develop a cure for HIV, focus is needed not only on the T cell compartment, but also on these myeloid reservoirs of persistent HIV infection. In this review, we summarize their importance when designing HIV cure strategies and challenges associated to their identification and specific targeting by the “shock and kill” approach.

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“…We demonstrate here that these deficiencies can be ameliorated in the newly developed NSG-SGM3 mice, which transgenically express three human cytokine/chemokine genes IL-3, GM-CSF, and KITLG. The expression of these genes improves the differentiation and maturation of the myeloid cells [25][26][27][28][29] . The present study is aimed at establishing a reliable new-generation, humanized mouse model for the HIV/Mtb co-infection research.…”

Section: Introductionmentioning

confidence: 99%

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

Bohórquez,

Adduri,

Ansari

et al. 2024

Preprint

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. Further, co-infections with HIV and Mtb have severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/Mtb infections. The present study was focused on developing a humanized mouse model for investigations on HIV-Mtb co-infection. Using NSG-SGM3 mice that can engraft human stem cells, our studies showed that they were able to engraft human CD34+ stem cells which then differentiate into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced the development of granulomatous lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Our results suggest that the humanized NSG-SGM3 mice are able to recapitulate the effects of HIV and Mtb infections and co-infection in the human host at pathological, immunological and metabolism levels, providing a dependable small animal model for studying HIV/Mtb co-infection.

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Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy

Cited by 11 publications

References 181 publications

The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?

The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?

HIV Latency in Myeloid Cells: Challenges for a Cure

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

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