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HIV-1 Vpr targets PU.1 to vastly alter the antiviral machinery of HIV infected primary human macrophages

GSE220574 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2024/04/30 Platform GPL24676
Summary
HIV-1 accessory protein, Vpr, is required for efficient HIV-1 infection of macrophages. Here we show that Vpr reprograms macrophage gene expression by altering the activity of master transcriptional regulator, PU.1, which is responsible for regulating the expression of host immune response genes and is necessary for normal hematopoiesis. In HIV-infected primary macrophages, Vpr-dependent changes in PU.1 levels result in suppression of known anti-viral targets of Vpr including IFITM3 and MRC1. Moreover, we find that PU.1 and its co-factor TET2 are co-recruited to DCAF1 by Vpr and targeted for accelerated degradation. Downmodulation of PU.1 is a highly conserved function of Vpr that is maintained across primate lentiviruses including HIV-2 and several SIVs. In contrast, this activity is not shared by the evolutionarily related accessory protein Vpx. Our findings demonstrate how Vpr dramatically enhances HIV spread in macrophages by targeting a myeloid-specific transcription factor needed for expression of multiple viral restriction factors.
Published in
HIV-1 Vpr combats the PU.1-driven antiviral response in primary human macrophages
Virgilio MC, Ramnani B, Chen T et al. · Nature communications 2024 · PMID 38951492 · doi:10.1038/s41467-024-49635-w
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Also filed as BioProject PRJNA910208. Searching any of these in the dataset finder brings you back here.

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