Impact of HIV-1 infection on the microglia transcriptome: induction of microRNA-23b leads to G3BP2-mediated stress granules assembly disruption
Microglia act as HIV reservoirs in the brain and contribute to the development of HIV-associated neurocognitive disorders despite antiretroviral therapy. We examined the transcriptome of primary microglia infected ex vivo with HIV-1. Analyses reveal a significant modulation of DNA damage/cell cycle-, cellular stress- and non-membrane bounded organelle assembly-related gene expression, and a broad effect on the microRNA profile. MicroRNA-23b is identified among upregulated microRNAs in HIV-1-infected microglia, and downregulated g3bp2 mRNA, validated as its target. G3BP2 is a core component of stress granules (SGs), which serve as antiviral and proinflammatory platforms. MicroRNA-23b mimics reduced both G3BP2 expression and SG assembly in stress-induced monocyte-derived microglial cells (MDMi), and few SGs aggregate in infected MDMi. Inhibition of MicroRNA-23b partially re-established SG formation and reduced HIV-1 replication. Thus, microRNA-23b induction contributes to HIV-1 strategies aimed at counteracting SG assembly in infected microglia, a host response that restricts HIV-1 replication and ensuing neuropathogenesis.