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

Abstract

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.

• Authors: Dejiang Zhou, Eliezer Masliah, Stephen A Spector
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 203 Issue 11 Pg. 1647-57 (Jun 01 2011) ISSN: 1537-6613 [Electronic] United States
• PMID: 21592995 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• HIV Envelope Protein gp120
• LAMP1 protein, human
• Lysosome-Associated Membrane Glycoproteins
• MAP1LC3A protein, human
• Macrolides
• Microtubule-Associated Proteins
• gp120 protein, Human immunodeficiency virus 1
• bafilomycin A1

Topics

• Adult
• Aged
• Autophagy (immunology, physiology)
• Autopsy
• Blotting, Western
• Case-Control Studies
• Cell Line, Tumor
• Encephalitis, Viral (immunology, metabolism, pathology, virology)
• Female
• Frontal Lobe (immunology, metabolism, pathology, virology)
• HIV Envelope Protein gp120 (pharmacology)
• HIV Infections (immunology, metabolism, pathology, virology)
• Humans
• Immunohistochemistry
• Lysosome-Associated Membrane Glycoproteins (metabolism)
• Lysosomes
• Macrolides (pharmacology)
• Male
• Microtubule-Associated Proteins (metabolism)
• Middle Aged
• Phagosomes