Failure to detect active virus replication in mast cells at various tissue sites of HIV patients by immunohistochemistry

Nelson, Ann Marie; Auerbach, Aaron; Man, Yan‐gao

doi:10.7150/ijbs.5.603

Cited by 16 publications

(11 citation statements)

References 21 publications

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“…The development of the NSG-SGM3-BLT model containing high levels of human myeloid cells including mast cells, particularly in the mucosal and connective tissues, now provides a potential model for defining the roles of mast cells in defense against key human pathogens, since mast cells have been suggested to provide anti-bacterial, anti-helminth and anti-viral responses to human-specific pathogens that cannot otherwise be studied in small animal models. Furthermore, the role of mast cells as a reservoir for HIV is a concept that has been suggested (33;34) , but remains uncertain (35) , and could be tested directly in this model.…”

Section: Discussionmentioning

confidence: 99%

Humanized mouse model of mast cell–mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis

Bryce

Falahati

Kenney

et al. 2016

Journal of Allergy and Clinical Immunology

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Background Mast cells are a critical component of allergic responses in humans, and animal models that allow the in vivo investigation of their contribution to allergy and evaluation of new human-specific therapeutics are urgently needed. Objective We have developed a new humanized mouse model that supports human mast cell engraftment and human IgE-dependent allergic responses. Methods This model is based on the NOD-scid IL2rgnull SCF/GM-CSF/IL3 (NSG-SGM3) strain of mice engrafted with human thymus, liver and hematopoietic stem cells (termed BLT). Results Large numbers of human mast cells develop in NSG-SGM3 BLT mice and populate the immune system, peritoneal cavity, and peripheral tissues. The human mast cells in NSG-SGM3 BLT mice are phenotypically similar to primary human mast cells and express CD117, tryptase, and FcεRI. These mast cells undergo degranulation in an IgE-dependent and independent manner, and can be readily cultured in vitro for additional studies. Intradermal priming of engrafted NSG-SGM3 mice with a chimeric IgE containing human constant regions resulted in development of a robust passive cutaneous anaphylaxis (PCA) response. Moreover, we describe the first report of a human mast cell antigen-dependent passive systemic anaphylaxis (PSA) response in primed mice. Conclusions NSG-SGM3 BLT mice provide a readily available source of human mast cells for investigation of mast cell biology and a pre-clinical model of PCA and PSA that can be used to investigate the pathogenesis of human allergic responses and to test new therapeutics prior to their advancement to the clinic.

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Section: Discussionmentioning

confidence: 99%

Humanized mouse model of mast cell–mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis

Bryce

Falahati

Kenney

et al. 2016

Journal of Allergy and Clinical Immunology

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“…In ART-suppressed individuals, two studies did not detect HIV-DNA in CD34+ progenitor cells[42,43], while a third found HIV-DNA in CD133+ bone marrow progenitor cells from 6/11 patients[44]. Bone marrow mast cell progenitors can be latently infected with HIV, and one study detected infected mast cells in some tissues of treated patients[45], although another study found no evidence of infected mast cells in multiple organs[46]. …”

Section: Bone Marrowmentioning

confidence: 99%

Tissue reservoirs of HIV

Wong

Yukl

2016

Current Opinion in HIV and AIDS

192

161

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Purpose Tissue reservoirs of HIV may promote the persistent immunopathology responsible for non-AIDS morbidity and data support multifocal reactivation from tissues as the source of viral rebound during ART interruption. The heterogeneity of tissue reservoirs and incomplete knowledge about their composition are obstacles to an HIV cure. Recent findings In addition to the higher concentration of infected CD4+ T cells found in both central lymphoid tissues and gut, specific subsets of CD4+ T cells appear to play a disproportionate role in HIV persistence. Recently, a subset of central memory T cells enriched in lymphnode germinal centers called T-follicular helper cells have been identified that express more viral RNA and occupy an anatomic niche inaccessible to CTL killing. Additional observations suggest that ARV concentrations may be lower in some tissues raising the possibility for localized, low-level viral replication. Finally, some recent data implicate the persistence of infected, non-CD4+ T cell types in tissues during ART. Summary The retention of infected cells in a wide variety of tissues, often with distinct viral and cellular characteristics, underscores the importance of studying tissue reservoirs in the development and assessment of cure strategies. Both inhibitory ARVs and latency reversing drugs must reach these sites and novel strategies may be needed to attack virus in cells as variable as Tfh and macrophages.

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“…However, a recent study could not detect active HIV-1 replication in tissue mast cells from ten donors [41*], suggesting that actively infected mast cells are rapidly cleared in successfully treated patients even though HIV-1 is not rapidly cytopathic in these cells [38*]. At present, long-term significance of the possible mast cell reservoir is unclear, and it is not known whether a mast cell reservoir exists in HAART-treated patients with undetectable viral loads.…”

Section: Mast Cell Progenitor Infectionmentioning

confidence: 99%

Hematopoietic stem/precursor cells as HIV reservoirs

McNamara

Collins

2011

Current Opinion in HIV and AIDS

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Purpose of Review Although latent HIV-1 infection in CD4+ T cells contributes to HIV persistence, there is mounting evidence that other viral reservoirs exist. Here, we review recent data suggesting that the infection of hematopoietic progenitor cells creates additional reservoirs for HIV in vivo. Recent Findings New studies suggest that some types of hematopoietic progenitor cells have the potential to generate reservoirs for HIV. This review focuses on two types that can be infected by HIV in vitro and in vivo: multipotent hematopoietic progenitor cells in the bone marrow and circulating mast cell progenitors. Of these two types, only CD34+ bone marrow cells have been shown to harbor latent provirus in HIV+ individuals with undetectable viral loads on HAART. Latent infection of these long-lived cell types may create a significant barrier to HIV eradication; indeed the potential infection of hematopoietic stem cells in particular could lead to an HIV reservoir that does not appreciably decay over the lifespan of the host. Summary To eradicate HIV infection, it will be necessary to purge all viral reservoirs in the host. The findings highlighted here suggest that multipotent hematopoietic progenitor cells and possibly tissue mast cells may constitute significant reservoirs for HIV that must be addressed in order to eliminate HIV infection. Future studies are needed to determine which types of CD34+ cells are infected in vivo and whether infected CD34+ cells contribute to residual viremia in people with undetectable viral loads on HAART.

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Failure to detect active virus replication in mast cells at various tissue sites of HIV patients by immunohistochemistry

Cited by 16 publications

References 21 publications

Humanized mouse model of mast cell–mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis

Humanized mouse model of mast cell–mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis

Tissue reservoirs of HIV

Hematopoietic stem/precursor cells as HIV reservoirs

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