Fig. 4: Overview of the roles of microglial activation and HIV-1 factors in NeuroHIV.

This figure illustrates the multifaceted roles of various brain cells in the pathogenesis of NeuroHIV, driven by HIV-1 factors and microglial activation: a Microglia activation: HIV-1 replication and transcription, the production of HIV-1 factors and associated miRNA, IncRNA and EVs, and proinflammatory cytokines, and interaction with other cells in the brain. b Neuron: neuronal death, endolysosomal dysfunction, and dendritic impairments, contributing to neurodegeneration; c The blood-brain barrier (BBB): reducing the expression of tight junction proteins, and inducing endothelial cell apoptosis. d Astrocytes: apoptosis, cellular senescence, and the release of proinflammatory cytokines; e Oligodendrocytes: apoptosis, myelin sheath damage, and white matter injury; Immune Cells: a proinflammatory environment in the brain; (f) Immune cells: the production of proinflammatory cytokines. Collectively, these cellular dysfunctions create a proinflammatory environment in the brain, leading to the spectrum of clinical manifestations of NeuroHIV, including dementia, mild neurocognitive disorder, and asymptomatic neurocognitive impairment.