Of mice, men, and HTLV-1

Dodon, Madeleine Duc

doi:10.1182/blood-2013-11-538272

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…Moreover, ATL xenograft mouse models do not provide answers to how HTLV-I induces ATL at early steps and how it maintains leukemogenesis (reviewed in Niewiesk, 2016 ). In this context, humanized mouse models were generated (reviewed in Panfil et al, 2013 ; Duc Dodon, 2014 ; Niewiesk, 2016 ) ( Table 1 ).…”

Section: Mouse Models Of Atlmentioning

confidence: 99%

“…In a different study, intra-bone marrow injection (IBMI) of cord blood CD133 + stem cells intratibialy into sublethally irradiated NSG mice was performed ( Tezuka et al, 2014 ). This study is based on the idea that CD133 + cells are believed to be the ancestral of CD34 + in hematopoiesis and carry the potential to differentiate to any hematopoietic cells including lymphocytes ( Tezuka et al, 2014 ; reviewed in Duc Dodon, 2014 ). One month following CD133 + inoculation, human CD45 + leukocytes were found to completely reconstitute the murine bone marrow.…”

Section: Mouse Models Of Atlmentioning

confidence: 99%

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Mouse Models That Enhanced Our Understanding of Adult T Cell Leukemia

et al. 2018

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Adult T cell Leukemia (ATL) is an aggressive lymphoproliferative malignancy secondary to infection by the human T-cell leukemia virus type I (HTLV-I) and is associated with a dismal prognosis. ATL leukemogenesis remains enigmatic. In the era of precision medicine in oncology, mouse models offer one of the most efficient in vivo tools for the understanding of the disease biology and developing novel targeted therapies. This review provides an up-to-date and comprehensive account of mouse models developed in the context of ATL and HTLV-I infection. Murine ATL models include transgenic animals for the viral proteins Tax and HBZ, knock-outs for key cellular regulators, xenografts and humanized immune-deficient mice. The first two groups provide a key understanding of the role of viral and host genes in the development of ATL, as well as their relationship with the immunopathogenic processes. The third group represents a valuable platform to test new targeted therapies against ATL.

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Section: Mouse Models Of Atlmentioning

confidence: 99%

Section: Mouse Models Of Atlmentioning

confidence: 99%

Mouse Models That Enhanced Our Understanding of Adult T Cell Leukemia

et al. 2018

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“…Mouse models have traditionally been cost-effective and easy to develop and maintain: however, HTLV-1 transmission in mice using usual methods of infection does not produce reliable infection and virus expression due to the inefficient fusion of HTLV-1 envelope with murine cells (Hajj et al 2012; Lairmore et al 2005). Hence, mice have been manipulated to establish HTLV-1 infection through the generation of transgenic and humanized mice models (Dodon 2014; Panfil et al 2013). The first humanized mouse model was generated by introducing the SCID mutation that impaired the development of mature B and T cells thus improving engraftment efficiency.…”

Section: Introductionmentioning

confidence: 99%

HTLV-1 Infection and Neuropathogenesis in the Context of Rag1-/-γc-/- (RAG1-Hu) and BLT Mice

Ginwala

Caruso

Khan

et al. 2017

J Neuroimmune Pharmacol

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To date, the lack of a suitable small animal model has hindered our understanding of Human T-cell lymphotropic virus (HTLV)-1 chronic infection and associated neuropathogenesis defined as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The host immune response plays a critical role in the outcome of HTLV-1 infection, which could be better tested in the context of humanized (hu) mice. Thus, we employ here the Balb/c-Rag1−/−γc−/− or Rag1 as well as Bone marrow-Liver-Thymic (BLT) mouse models for engraftment of human CD34+ hematopoietic stem cells. Flow cytometry and histological analyses confirmed reconstitution of Rag1 and BLT mice with human immune cells. Following HTLV-1 infection, proviral load (PVL) was detected in the blood of Rag-1 and BLT hu-mice as early as 2 weeks post-infection (wpi) with sustained elevation in the subsequent weeks followed by Tax expression. Additionally, infection was compared between adult and neonatal Rag1 mice with both PVL and Tax expression considerably higher in the adult Rag1 mice as compared to the neonates. Establishment of peripheral infection led to lymphocytic infiltration with concomitant Tax expression and resulting myelin disruption within the central nervous system of infected mice. In addition, up-regulation in the expression of several immune checkpoint mediators such as programmed cell death-1 (PD-1), T-cell Ig and ITIM domain (TIGIT), and T cell Ig and mucin domain-3 protein (Tim-3) were observed on CD8+ T cells in various organs including the CNS of infected hu-mice. Collectively, these studies represent the first attempt to establish HTLV-1 neuropathogenesis in the context of Rag-1 and BLT hu-mice as potential novel tools for understanding HTLV-1 neuropathogenesis and testing of novel therapies such as immune checkpoint blockade in the amelioration of chronic HTLV-1 infection.

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Humanized mice in infectious diseases

Ernst

2016

Comparative Immunology, Microbiology and Infectious Diseases

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Of mice, men, and HTLV-1

Cited by 3 publications

References 9 publications

Mouse Models That Enhanced Our Understanding of Adult T Cell Leukemia

Mouse Models That Enhanced Our Understanding of Adult T Cell Leukemia

HTLV-1 Infection and Neuropathogenesis in the Context of Rag1-/-γc-/- (RAG1-Hu) and BLT Mice

Humanized mice in infectious diseases

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