关键词: HIV相关的神经认知功能障碍, 艾滋病, 活性氧, 人类免疫缺陷病毒, 线粒体, 线粒体DNA, 8-氧鸟嘌呤

Abstract: Objective Oxidative stress has been suggested to play a key role in the neuropathogenesis of HIV infection. HIV proteins (gp120, Tat), and proinflammatory cytokines can trigger the production of reactive oxygen species (ROS), resulting in DNA and RNA lesions. Among all the lesions induced by ROS, one of the most frequently occured lesions in DNA and RNA is 8-hydroxydeoxyguanosine (8-oxoG). Here, we report accumulated DNA oxidative damage induced by ROS in the central nervous system (CNS) in tissue from neuro-AIDS patients. Methods The frontal cortex of autopsy tissue from HIV-1 infected patients was adopted for analysis for HIV-1 subtype, nuclear and mitochondrial DNA lesions by immunofluorescence staining, qPCR and sequencing of PCR cloning. Results This study provides evidence that HIV infection in the CNS leads to nuclear and mitochondrial genomic DNA damage in the brain. High level of nuclear and mtDNA 8-oxoG damage were identified in the cortex autopsy tissue of HIV-associated neurocognitive disorder (HAND) patients. Increased accumulation of mtDNA mutations and depletion occurs in brain tissue in a subset of HAND cases, and is significantly different from that observed in control cases. Conclusion These findings suggest that higher level of ROS in the CNS of HAND patients would contribute to the HIV induced neuro-inflammation and apoptosis of neuronal and glial cells.

Key words: HIV-1 associated neurocognitive disorders, acquired immune deficiency syndrome, reactive oxygen species, human immunodeficiency virus, mitochondria, mtDNA, 8-hydroxyguanine