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Extracellular vesicles carrying HIV-1 Nef induce long-term hyperreactivity of myeloid cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214959 | GEO | 2022/10/09

REPOSITORIES: GEO

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Extracellular vesicles carrying HIV-1 Nef induce long-term hyperreactivity of myeloid cells [ATAC-Seq]

Project description:A possible explanation for chronic inflammation in HIV-infected individuals treated with anti-retroviral therapy is hyperreactivity of myeloid cells due to a phenomenon called ‘trained immunity’. Here, we demonstrate that human monocyte-derived macrophages originating from monocytes initially treated with extracellular vesicles containing HIV-1 protein Nef (exNef), but differentiating in the absence of exNef, released increased levels of pro-inflammatory cytokines after lipopolysaccharide stimulation. This effect was associated with epigenetic changes related to inflammation and cholesterol metabolism pathways, upregulation of the lipid rafts, and was blocked by methyl-beta-cyclodextrin, statin, and by an inhibitor of the lipid raft-associated receptor IGF1R. Bone marrow-derived macrophages from exNef-injected mice, as well as from mice transplanted with bone marrow from exNef-injected animals, produced elevated levels of TNFalpha upon stimulation. These phenomena are consistent with exNef-induced trained immunity that may contribute to persistent inflammation and associated co-morbidities in HIV-infected individuals with undetectable HIV load.

2022-10-09 | GSE214958 | GEO

Extracellular vesicles carrying HIV-1 Nef induce long-term hyperreactivity of myeloid cells [RNA-Seq]

2022-10-09 | GSE214957 | GEO

HIV-Nef and ADAM17-Containing Plasma Extracellular Vesicles Induce and Correlate with Immune Pathogenesis in Chronic HIV Infection.

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HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity.

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Extracellular vesicles carrying lactate dehydrogenase induce suicide in increased population density of Plasmodium falciparum in vitro.

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HIV-1 Nef changes the proteome of T cells extracellular vesicles

Project description:Extracellular vesicles (EVs) are biomolecule carriers for intercellular communication in health and disease. Nef is a human immunodeficiency virus (HIV) virulence factor that is released from cells within EVs and is present in plasma EVs of HIV-1 infected individuals. We performed a quantitative proteomic analysis to fully characterize the Nef-induced changes in protein composition of T cell-derived EVs and identify novel host targets of HIV. Several proteins with well-described roles in infection or not previously associated with HIV pathogenesis were specifically modulated by Nef in EVs. Among the downregulated proteins are the interferon-induced transmembrane 1, 2 and 3 proteins (IFITM1-3), broad-spectrum antiviral factors known to be cell-to-cell transferable by EVs. Our data establish Nef as a modulator of EVs' global protein content and as an HIV factor that antagonizes IFITMs.

2024-01-26 | PXD041028 | Pride

HIV-1 Nef Protein Affects Cytokine and Extracellular Vesicles Production in the GEN2.2 Plasmacytoid Dendritic Cell Line.

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Inflammatory Stroke Extracellular Vesicles Induce Macrophage Activation.

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Allosteric loss-of-function mutations in HIV-1 Nef from a long-term non-progressor.

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