HIV-1 Nef Generates Lasting Innate Immune Memory in Haematopoietic Stem and Progenitor Cells In Vivo

ABSTRACT: HIV infection is accompanied by chronic inflammation-related co-morbidities, even when viral replication is suppressed by therapy. This persistent inflammatory state suggests that long-lived immune cell lineages may acquire stable pro-inflammatory programming. Here, we investigate whether inflammatory programming can be imprinted within haematopoietic lineages, following the exposure of mice and bone marrow-derived macrophages (BMDMs) to extracellular vesicles (EVs) carrying Nef, a key inflammatory factor of HIV. Multi-omics profiling shows that haematopoietic cells exposed to Nef-EVs undergo epigenetic remodelling and reprogramming of energy and lipid metabolism characteristic of trained innate immunity. The inflammatory phenotype in BMDMs is partially reversed by inhibition of glycolysis

SUBMITTER: Andrew Fleetwood 

PROVIDER: S-SCDT-10_1038-S44319-026-00838-W | biostudies-other |

REPOSITORIES: biostudies-other