Infection of the SCID-hu Mouse by HIV-1

Namikawa, Reiko; Kaneshima, Hideto; Lieberman, Miriam; Il, Weissman; McCune, JM

doi:10.1126/science.3201256

Cited by 337 publications

(176 citation statements)

References 26 publications

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Section: Wwwannualreviewsorg • How One Thing Led To Anothermentioning

confidence: 99%

“…All three efforts succeeded, and rapidly (143). Pathogenic patient HIV clones infected the SCID-hu mice and led to drops in CD4 counts (143), while the cloned isolates such as the Gallo and Montagnier HIV failed to infect the mice. We later concluded that the absolute CD4 dependency of HIV was in part an artifact of growing the virus on in vitro CD4 + T cells, and at SyStemix showed that commercially available soluble CD4 did not prevent pathogenic patient HIV infection.…”

Section: Wwwannualreviewsorg • How One Thing Led To Anothermentioning

confidence: 99%

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How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a “don't eat me” signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.

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Section: Wwwannualreviewsorg • How One Thing Led To Anothermentioning

confidence: 99%

Section: Wwwannualreviewsorg • How One Thing Led To Anothermentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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“…HIV-1 infection models have been widely used for the analysis of disease mechanisms and the development of anti-HIV-1 drugs, 61 as HIV-1 infects human T cells in SCID-hu mice. 26,62,63 This research is further accelerated through the use of HSC-transplanted immunodeficient mice, in which multilineage hematopoietic cells can be differentiated. [64][65][66][67] In this field, a unique model for HIV-1 [68][69][70] reported by Garcia's group at the University of North Carolina and termed bone marrow-liver-thymus (BLT) mice, has attracted attention.…”

Section: Infectious Diseasesmentioning

confidence: 99%

Current advances in humanized mouse models

et al. 2012

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Humanized mouse models that have received human cells or tissue transplants are extremely useful in basic and applied human disease research. Highly immunodeficient mice, which do not reject xenografts and support cell and tissue differentiation and growth, are indispensable for generating additional appropriate models. Since the early 2000s, a series of immunodeficient mice appropriate for generating humanized mice has been successively developed by introducing the IL-2Rc null gene (e.g., NOD/SCID/cc null and Rag2 null cc null mice). These strains show not only a high rate of human cell engraftment, but also generate well-differentiated multilineage human hematopoietic cells after human hematopoietic stem cell (HSC) transplantation. These humanized mice facilitate the analysis of human hematology and immunology in vivo. However, human hematopoietic cells developed from HSCs are not always phenotypically and functionally identical to those in humans. More recently, a new series of immunodeficient mice compensates for these disadvantages. These mice were generated by genetically introducing human cytokine genes into NOD/SCID/cc null and Rag2 null cc null mice. In this review, we describe the current knowledge of human hematopoietic cells developed in these mice. Various human disease mouse models using these humanized mice are summarized.

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“…Efforts to genetically engineer rodents to become HIV targets (e.g., artificial expression of human CD4, CCR5, or CXCR4) have largely failed, because, even if infection in vitro was achieved, HIV replication in vivo was limited or absent (1,6,7). Thus, substitute xenochimeric models have been developed by transplanting immunodeficient mice with either human peripheral blood leukocytes (hu-PBL-SCID) (8,9) or pieces of human fetal tissues containing hematopoietic cells (SCIDhu) (10,11). Both hu-PBL-SCID and SCID-hu mice sustain HIV infection and replication in vivo.…”

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confidence: 99%

Disseminated and sustained HIV infection in CD34⁺cord blood cell-transplanted Rag2^−/−γ_c^−/−mice

Baenziger¹,

Tussiwand²,

Schlaepfer³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

214

206

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Because of species selectivity, HIV research is largely restricted to in vitro or clinical studies, both limited in their ability to rapidly assess new strategies to fight the virus. To prospectively study some aspects of HIV in vivo, immunodeficient mice, transplanted with either human peripheral blood leukocytes or human fetal tissues, have been developed. Although these are susceptible to HIV infection, xenoreactivity, and short infection spans, resource and ethical constraints, as well as biased HIV coreceptor tropic strain infection, pose substantial problems in their use. Rag2 ؊/؊ ␥c ؊/؊ mice, transplanted as newborns with human CD34 ؉ cells, were recently shown to develop human B, T, and dendritic cells, constituting lymphoid organs in situ. Here we tested these mice as a model system for HIV-1 infection. HIV RNA levels peaked to up to 2 ؋ 10 6 copies per milliliter of plasma early after infection, and viremia was observed for up to 190 days, the longest time followed. A marked relative CD4 ؉ T cell depletion in peripheral blood occurred in CXCR4-tropic strain-infected mice, whereas this was less pronounced in CCR5-tropic strain-infected animals. Thymus infection was almost exclusively observed in CXCR4-tropic strain-infected mice, whereas spleen and lymph node HIV infection occurred irrespective of coreceptor selectivity, consistent with respective coreceptor expression on human CD4 ؉ T cells. Thus, this straightforward to generate and cost-effective in vivo model closely resembles HIV infection in man and therefore should be valuable to study virus-induced pathology and to rapidly evaluate new approaches aiming to prevent or treat HIV infection.

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Infection of the SCID-hu Mouse by HIV-1

Cited by 337 publications

References 26 publications

How One Thing Led to Another

How One Thing Led to Another

Current advances in humanized mouse models

Disseminated and sustained HIV infection in CD34⁺cord blood cell-transplanted Rag2^−/−γ_c^−/−mice

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Infection of the SCID-hu Mouse by HIV-1

Cited by 337 publications

References 26 publications

How One Thing Led to Another

How One Thing Led to Another

Current advances in humanized mouse models

Disseminated and sustained HIV infection in CD34+cord blood cell-transplanted Rag2−/−γc−/−mice

Contact Info

Product

Resources

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Disseminated and sustained HIV infection in CD34⁺cord blood cell-transplanted Rag2^−/−γ_c^−/−mice