Branton, W. | Search bioRxiv

bioRxiv2026

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.

microbiology↗

bioRxiv2020

Nodosome inhibition as a novel broad-spectrum antiviral strategy against arboviruses and SARS-CoV-2

In the present report, we describe two small molecules with broad-spectrum antiviral activity. These drugs block formation of the nodosome. The studies were prompted by the observation that infection of human fetal brain cells with Zika virus (ZIKV) induces expression of nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a host factor that was found to promote ZIKV replication and spread. A drug that targets NOD2 was shown to have potent broad-spectrum antiviral activity against other flaviviruses, alphaviruses and SARS-CoV-2, the causative agent of COVID-19. Another drug that inhibits the receptor-interacting serine/threonine-protein kinase 2 (RIPK2) which functions downstream of NOD2, also decreased replication of these pathogenic RNA viruses. The broad-spectrum action of nodosome targeting drugs is mediated, at least in part, by enhancement of the interferon response. Together, these results suggest that further preclinical investigation of nodosome inhibitors as potential broad-spectrum antivirals is warranted.

microbiology↗