HIV-1 infection and pathogenesis in a novel humanized mouse model

Zhang, Liguo; Kovalev, Grigoriy I.; Su, Lishan

doi:10.1182/blood-2006-07-033159

Cited by 128 publications

(143 citation statements)

References 25 publications

(29 reference statements)

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“…At the forefront of this research is the evaluation of the role of Treg cells in both viral clearance mechanisms and immune-pathology described in chronic HIV infection. An earlier study from our lab demonstrated HIV infection in the BALB/c-DKO-hu mouse model mimicked infection in HIV + patients, namely an increase in viral load followed by a subsequent depletion of CD4 + T cells and an inversion of the CD4 + /CD8 + Tcell ratio in the peripheral blood [123]. Both naïve and memory subsets (CD45RO + and CD45RO − ) of CD4 + T cells were infected in lymphoid organs similar to HIV-infected patients [127].…”

Section: Hiv-1 Pathogenesis In the Humanized Mouse Modelmentioning

confidence: 99%

“…Several groups including our own have demonstrated the efficient use of the BALB/c-DKOhu HSC model for HIV infection utilizing either cord-blood or fetal liver CD34 + cells [121][122][123]. Although all groups were able to show infection of HIV (both CCR5-and CXCR4-tropic virus) in peripheral blood, long term viremia, and depletion of CD4 + T-cell populations similar to HIV-infected patients, they were unable to demonstrate appreciable levels of anti-HIV antibody responses.…”

Section: Emerging Humanized Mouse Models For the Study Of Hiv Infectimentioning

confidence: 99%

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Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis

et al. 2008

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FoxP3 + CD4 + CD25 + regulatory T (Treg) cells are implicated in a number of pathologic processes including elevated levels in cancers and infectious diseases, and reduced levels in autoimmune diseases. Treg cells are activated to modulate immune responses to avoid over-reactive immunity. However, conflicting findings are reported regarding relative levels of Treg cells during HIV-1 infection and disease progression. The role of Treg cells in HIV-1 diseases (aberrant immune activation) is poorly understood due to lack of a robust model. We summarize here the regulation and function of Foxp3 in Treg cells and in modulating HIV-1 replication. Based on recent findings from SIV/monkey and HIV/humanized mouse models, a model of the dual role of Treg cells in HIV-1 infection and immuno-pathogenesis is discussed. KeywordsRegulatory T cells; AIDS; Chromatin; Epigenetic; Humanized mouse; DKO-hu; ONTAK Regulatory T cells play an important role in self immune tolerance and in balanced immune responsesThe regulation of immune tolerance is a critical aspect of immunology. The balance between recognition of self versus non-self is essential for maintenance of immune homeostasis. Regulatory T cells (CD4 + CD25 + ) are a crucial component for the control of deleterious effects from excessive immune responses as seen in autoimmune disease or allergic insult [1,2]. Treg cells have been implicated in a number of pathologic processes including elevated levels in cancers [3][4][5] and infectious diseases [6][7][8][9], and reduced levels in autoimmune diseases [1,[10][11][12][13]. It is apparent that Treg cells are induced (or recruited and expanded) by most infections to modulate host immune responses to avoid overreactive immunity (Fig. 1). As a result, Treg play a critical role in immune responses, vaccinations as well as in immunopathogenesis of pathogens. For example, Leishmania infection leads to induction of Treg that help to maintain the balance of immune response and pathogen persistence [18,19]. For the host, persistence of the pathogen is beneficial to maintain effective immunity against these pathogens [18]. In a number of chronic viral infections, Treg are induced to subdue the anti-viral immune responses and allow persistent infection. Mechanisms of CD4 T-cell differentiationT-cell lineage commitment and activation of T cells are usually accompanied by changes in patterns of gene expression. During T-cell responses, T helper (Th) progenitor cells will undergo Th1 or Th2 lineage commitments involving well-defined initiation cytokines, transcription factors, and effector cytokines. Expression of T-bet and GATA3 in Th1 and Th2 cells, respectively, is epigenetically regulated by histone modification and DNA methylation. As T lineage determinants, T-bet or GATA3 are also involved in epigenetically reprogramming the T-cell genome to silence the Th2 or Th1 effector cytokines, respectively, and to activate Th1 or Th2 cytokine genes for transcription (Fig. 2). Similarly, Th17 cell differentiation requires IL-6/TGF-β (mo...

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Section: Hiv-1 Pathogenesis In the Humanized Mouse Modelmentioning

confidence: 99%

Section: Emerging Humanized Mouse Models For the Study Of Hiv Infectimentioning

confidence: 99%

Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis

et al. 2008

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“…In this context, humanized mouse models that have a closer resemblance to the human immune system could offer great benefits in pre-clinical research by lessening type 1 and type 2 errors made by a wrongful extrapolation of results obtained from common animal models. Humanized mouse models have already been extensively employed in research of cancer and human-specific viruses, such as HIV and herpes (110)(111)(112), however, their use in bacterial pneumonia models is not well established. A humanized bacterial pneumonia model could offer significant advantages over wild type animals.…”

Section: Humanized Modelsmentioning

confidence: 99%

Animal models of hospital-acquired pneumonia: current practices and future perspectives

Bielen¹,

Jongers²,

Malhotra-Kumar³

et al. 2017

Ann. Transl. Med.

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Lower respiratory tract infections are amongst the leading causes of mortality and morbidity worldwide. Especially in hospital settings and more particularly in critically ill ventilated patients, nosocomial pneumonia is one of the most serious infectious complications frequently caused by opportunistic pathogens.Pseudomonas aeruginosa is one of the most important causes of ventilator-associated pneumonia as well as the major cause of chronic pneumonia in cystic fibrosis patients. Animal models of pneumonia allow us to investigate distinct types of pneumonia at various disease stages, studies that are not possible in patients.Different animal models of pneumonia such as one-hit acute pneumonia models, ventilator-associated pneumonia models and biofilm pneumonia models associated with cystic fibrosis have been extensively studied and have considerably aided our understanding of disease pathogenesis and testing and developing new treatment strategies. The present review aims to guide investigators in choosing appropriate animal pneumonia models by describing and comparing the relevant characteristics of each model using P. aeruginosa as a model etiology for hospital-acquired pneumonia. Key to establishing and studying these animal models of infection are well-defined end-points that allow precise monitoring and characterization of disease development that could ultimately aid in translating these findings to patient populations in order to guide therapy. In this respect, and discussed here, is the development of humanized animal models of bacterial pneumonia that could offer unique advantages to study bacterial virulence factor expression and host cytokine production for translational purposes.

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“…Long-term functional engraftment of a human immune system was achieved in immune deficient mice reconstituted with human hematopoietic stem cells (HSC) in divergent genetic backgrounds: NOD/scid-IL-2R␥ c null (NSG), [7][8][9][10] BALB/c-Rag2 Ϫ/Ϫ ␥ c Ϫ/Ϫ (BRG), [11][12][13][14][15] and NOD/ scid mice reconstituted with fetal thymus/liver and HSC (BLT). 16,17 Despite rapid research advances made in these rodent animal models on HIV-1 disease pathobiology, their importance for studies of HIV-1-related complications, including neuroAIDS, have not been explored.…”

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confidence: 99%