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Extracellular vesicles carrying HIV-1 Nef induce trained immunity in myeloid cells

Dubrovsky, L.; Brichacek, B.; Prashant, N. M.; Pushkarsky, T.; Mukhamedova, N.; Dragoljevic, D.; Fitzgerald, M.; Horvath, A.; Murphy, A. J.; Sviridov, D.; Bukrinsky, M. I.

2022-06-28 immunology
10.1101/2022.06.24.497538 bioRxiv
Show abstract

SummaryPersistent inflammation is a hallmark of HIV infection and is not reversed after suppression of viral replication by anti-retroviral therapy (ART). One explanation for chronic inflammation in ART-treated HIV-infected individuals is hyperreactivity of the 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 inhibitor of activity of lipid raft-associated receptor IGF1R. Bone marrow-derived macrophages from exNef-injected mice had higher abundance of lipid rafts and produced elevated levels of TNF. These phenomena are consistent with trained immunity and may contribute to persistent inflammation and co-morbidities in HIV-infected individuals.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.