HIV-1 Nef programs long-lasting innate immune memory in hematopoietic stem and progenitor cells in a mouse model

It is often assumed that a complete cure would resolve this inflammation; however its origin and mechanisms may be more complex and not entirely dependent on the continuous presence of the virus. To investigate whether inflammatory programming can be imprinted in hematopoietic cells, we treated mice with extracellular vesicles containing the HIV protein Nef (exNef), a major viral pathogenic and inflammatory factor.

Using a multi-omics approach, we found that haematopoietic cells exposed to exNef displayed epigenetic modifications and reprogramming of energy and lipid metabolism pathways characteristic of trained innate immunity (TRIM).