Association of Cytokines With Exosomes in the Plasma of HIV-1–Seropositive Individuals

Konadu, Kateena Addae; Chu, Jane; Huang, Ming-Bo; Amancha, Praveen Kumar; Armstrong, Wendy S.; Powell, Michael D.; Villinger, François; Bond, Vincent C.

doi:10.1093/infdis/jiu676

Cited by 84 publications

(90 citation statements)

References 14 publications

(20 reference statements)

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“…6 ). Nevertheless, we also expect EVs to carry many other proliferative miRNAs, as observed in small-RNA seq analysis, along with proteins and transcription factors (19, 79) such as HIF-1α, cytokines (80), and growth factors that may contribute to enhanced proliferation of cells. Overall, our study underscores the role of communication between HIV-1–infected inflammatory cell–derived EVs and uninfectable pulmonary vascular cells in HIV PAH pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Macrophage‐derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse

Sharma¹,

Chinnappan²,

Agarwal³

et al. 2018

FASEB j.

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Our previous studies consistently demonstrate enhanced pulmonary vascular remodeling in HIV–infected intravenous drug users, and in simian immunodeficiency virus–infected macaques or HIV-transgenic rats exposed to opioids or cocaine. Although we reported an associated increase in perivascular inflammation, the exact role of inflammatory cells in the development of pulmonary vascular remodeling remains unknown. In this study, HIV–infected and cocaine (H+C)–treated human monocyte derived macrophages released a higher number of extracellular vesicles (EVs), compared to HIV-infected or uninfected cocaine-treated macrophages, with a significant increase in the particle size range to 100–150 nm. Treatment of primary human pulmonary arterial smooth muscle cells (HPASMCs) with these EVs resulted in a significant increase in smooth muscle proliferation. We also observed a significant increase in the miRNA-130a level in the EVs derived from H+C-treated macrophages that corresponded with the decrease in the expression of phosphatase and tensin homolog and tuberous sclerosis 1 and 2 and activation of PI3K/protein kinase B signaling in HPASMCs on addition of these EVs. Transfection of HPASMCs with antagomir-130a–ameliorated the EV-induced effect. Thus, we conclude that EVs derived from H+C-treated macrophages promote pulmonary smooth muscle proliferation by delivery of its prosurvival miRNA cargo, which may play a crucial role in the development of PAH.—Sharma, H., Chinnappan, M., Agarwal, S., Dalvi, P., Gunewardena, S., O’Brien-Ladner, A., Dhillon, N. K. Macrophage-derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse.

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Section: Discussionmentioning

confidence: 99%

Macrophage‐derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse

Sharma¹,

Chinnappan²,

Agarwal³

et al. 2018

FASEB j.

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“…55 A recent study demonstrated that exosomes are also enriched in cytokines in the plasma of HIV-positive individuals relative to the negative controls. 56 These studies provide a basis for exosomes as biomarkers for HIV infection. Elegant work from the study by Sampey et al 137 using hydrogel nanotrap particles as affinity baits, has demonstrated the capture of HIV-1 virions, HIV proteins and exosomes-containing TAR-RNA in the patient serum.…”

Section: Hiv Infection Alters Exosomal Release and Compositionmentioning

confidence: 96%

Emerging roles of extracellular vesicles in neurodegenerative disorders: focus on HIV-associated neurological complications

Lü

Cai

et al. 2016

Cell Death Dis

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Exosomes are membrane-enriched extracellular vesicles with a proposed diameter in the range of 30–100 nm. They are released during both normal homeostasis as well as under pathological conditions by most cell types. In recent years, there has been robust interest in the study of these vesicles as conduits for the delivery of information between cells in both analogous as well as disparate tissues. Their ability to transport specialized cargo including signaling mediators, proteins, messenger RNA and miRNAs characterizes these vesicles as primary facilitators of cell-to-cell communication and regulation. Exosomes have also been demonstrated to have important roles in the field of cancer biology and metastasis. More recently, their role in several neurodegenerative disorders has been gaining increased momentum as these particles have been shown to promote the spread of toxic factors such as amyloid beta and prions, adding further validity to their role as important regulators of disease pathogenesis. This review briefly summarizes current findings and thoughts on exosome biology in the context of neurodegenerative disorders and the manipulation of these particles for the development of potential therapeutic strategies.

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“…Plasma was collected from whole blood of human donors into tubes containing ethylenediaminetetraacetic acid (EDTA) and processed as described by Konadu et al 23 with some modifications. Whole-blood samples were centrifuged at 3,500 rpm for 10 min at 4°C.…”

Section: Isolation Of Human Plasma-derived Exosomesmentioning

confidence: 99%

“…We also isolated exosomes from human breast milk and human plasma using published methods. 15,23 To confirm successful exosome isolation, we performed a series of SDS-PAGE and Western blot analyses to examine expression of well-known exosomal proteins ( Figure 1A and B). Specifically, breast milk exosomes incubated with anti-clathrin and -CD9 antibodies yielded protein bands at 180 kDa and 28 kDa, respectively ( Figure 1A1 and A2).…”

Section: Isolation and Characterization Of Exosomesmentioning

confidence: 99%

Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells

Sims

Farrow

Williams

et al. 2017

IJN

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Exosomes, 30–200 nm nanostructures secreted from donor cells and internalized by recipient cells, can play an important role in the cellular entry of some viruses. These microvesicles are actively secreted into various body fluids, including blood, urine, saliva, cerebrospinal fluid, and breast milk. We successfully isolated exosomes from human breast milk and plasma. The size and concentration of purified exosomes were measured by nanoparticle tracking, while Western blotting confirmed the presence of the exosomal-associated proteins CD9 and CD63, clathrin, and T cell immunoglobulin and mucin proteins (TIMs). Through viral infection assays, we determined that HIV-1 utilizes an exosome-dependent mechanism for entry into human immune cells. The virus contains high amounts of phosphatidylserine (PtdSer) and may bind PtdSer receptors, such as TIMs. This mechanism is supported by our findings that exosomes from multiple sources increased HIV-1 entry into T cells and macrophages, and viral entry was potently blocked with anti-TIM-4 antibodies.

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Association of Cytokines With Exosomes in the Plasma of HIV-1–Seropositive Individuals

Cited by 84 publications

References 14 publications

Macrophage‐derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse

Macrophage‐derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse

Emerging roles of extracellular vesicles in neurodegenerative disorders: focus on HIV-associated neurological complications

Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells

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