Autophagy is increased in postmortem brains of persons with HIV-1-associated encephalitis.

BACKGROUND: Autophagy is critical to maintaining cell homeostasis and is implicated in neurodegenerative diseases. This research examined the role of autophagy in human immunodeficiency virus type 1 (HIV-1)-associated encephalitis, the pathologic hallmark of neuroAIDS.

METHODS: The frontal cortex from 32 HIV-infected persons (12 without evidence HIV-1 encephalitis or clinical signs of central nervous system impairment and 20 with histopathological findings of HIV-1 encephalitis) and 8 persons without HIV infection and any neuropathology were examined postmortem. Green fluorescent protein-labeled (GFP) light chain 3 (LC3)-expressing neuroblastoma SK-N-SH cells treated with gp120 from CXCR4 and CCR5 viruses were also examined. Autophagic markers were assessed by means of Western blot analysis, transmission electron microscopy (TEM), and confocal microscopy.

RESULTS: Autophagic proteins Beclin 1, Autophagy-related gene (Atg)-5, Atg-7, and LC3-II were significantly increased in brains with HIV-1 encephalitis (P < .05). These findings were confirmed by TEM and immunostaining of brain tissue. Additionally, levels of autophagic proteins and autophagosomes were increased in neuronal cells treated with both CXCR4- or CCR5-tropic HIV-1 gp120. No increase in the level of autophagy was observed in the brains of HIV-infected persons without HIV-1 encephalitis compared with the level in brains of HIV-uninfected persons.

CONCLUSIONS: Postmortem brains with HIV-1 encephalitis exhibit increased markers of autophagy compared with brains from HIV-infected persons without HIV-1 encephalitis or HIV-uninfected control brains, which suggests that dysregulation of autophagy may be important in the pathogenesis of neuroAIDS.