ArticleRetrovirology2013
HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model.
Article in Retrovirology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed.
- Review
- The decay of HIV under anti-retroviral therapy is biphasic even in humanized mice with just T cells.Journal of virology · 2026Article
- Human Immune System Reconstitution in NOD/Shi-Life (Basel, Switzerland) · 2025Article
- A germ-free humanized mouse model shows the contribution of resident microbiota to human-specific pathogen infection.Nature biotechnology · 2024Article
- The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?Pathogens (Basel, Switzerland) · 2023Review
- Advancing basic and translational research to deepen understanding of the molecular immune-mediated mechanisms regulating long-term persistence of HIV-1 in microglia in the adult human brain.Journal of leukocyte biology · 2022Review
- Inducing Long-Term HIV-1 Latency in the TKO-BLT Mouse Model.Methods in molecular biology (Clifton, N.J.) · 2022Article
- HIV-1 and drug abuse comorbidity: Lessons learned from the animal models of NeuroHIV.Neuroscience letters · 2021Review
- The Interplay of HIV-1 and Macrophages in Viral Persistence.Frontiers in microbiology · 2021Review
- μ-Lat: A mouse model to evaluate human immunodeficiency virus eradication strategies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- The Paradox of HIV Blood-Brain Barrier Penetrance and Antiretroviral Drug Delivery Deficiencies.Trends in neurosciences · 2020Review
- The Establishment of an In Vivo HIV-1 Infection Model in Humanized B-NSG Mice.Virologica Sinica · 2020Article
- Article
- Humanized Mouse Model of HIV-1 Latency with Enrichment of Latent Virus in PD-1Journal of virology · 2019Article
- Article
- Recent Updates on Mouse Models for Human Immunodeficiency, Influenza, and Dengue Viral Infections.Viruses · 2019Review
- Alveolar Macrophage Dysfunction and Increased PD-1 Expression During Chronic SIV Infection of Rhesus Macaques.Frontiers in immunology · 2019Article
- Review
- T cells establish and maintain CNS viral infection in HIV-infected humanized mice.The Journal of clinical investigation · 2018Article
- Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
backgroundThe major targets of HIV infection in humans are CD4⁺ T cells. CD4⁺ T cell depletion is a hallmark of AIDS. Previously, the SCID-hu thy/liv model was used to study the effect of HIV on thymopoeisis in vivo. However, these mice did not develop high levels of peripheral T cell reconstitution and required invasive surgery for infection and analysis. Here, we describe a novel variant of this model in which thy/liv implantation results in systemic reconstitution with human T cells in the absence of any other human hematopoietic lineages.
resultsNOD/SCID-hu thy/liv and NSG-hu thy/liv mice were created by implanting human fetal thymus and liver tissues under the kidney capsule of either NOD/SCID or NSG mice. In contrast to NOD/SCID-hu thy/liv mice that show little or no human cells in peripheral blood or tissues, substantial systemic human reconstitution occurs in NSG-hu thy/liv. These mice are exclusively reconstituted with human T cells (i.e. T-cell only mice or TOM). Despite substantial levels of human T cells no signs of graft-versus-host disease (GVHD) were noted in these mice over a period of 14 months. TOM are readily infected after parenteral exposure to HIV-1. HIV replication is sustained in peripheral blood at high levels and results in modest reduction of CD4⁺ T cells. HIV-1 replication in TOM responds to daily administration of combination antiretroviral therapy (ART) resulting in strong suppression of virus replication as determined by undetectable viral load in plasma. Latently HIV infected resting CD4⁺ T cells can be isolated from suppressed mice that can be induced to express HIV ex-vivo upon activation demonstrating the establishment of latency in vivo.
conclusionsNSG-hu thy/liv mice are systemically reconstituted with human T cells. No other human lymphoid lineages are present in these mice (i.e. monocytes/macrophages, B cells and DC are all absent). These T cell only mice do not develop GVHD, are susceptible to HIV-1 infection and can efficiently maintain virus replication. HIV infected TOM undergoing ART harbor latently infected, resting CD4+ T cells.
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