Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains

Area of Science:

• Neuroscience
• Immunology
• Virology

Background:

• HIV encephalitis causes neurological damage despite minimal direct neuronal infection.
• Macrophages are the primary infected cells in the brain, releasing factors that may cause damage.
• Cerebrospinal fluid (CSF) analysis of immune factors has not correlated with HIV encephalitis severity.

Purpose of the Study:

• To investigate the concentrations of HIV p24, quinolinic acid (QUIN), and various cytokines (IL-1, IL-3, IL-6, TNF-alpha, GMCSF) directly within brain tissue.
• To correlate these tissue concentrations with the severity of HIV encephalitis.
• To determine the role of these factors in the etiology of HIV-related neurologic dysfunction.

Main Methods:

• Analysis of brain tissue homogenates from 10 AIDS autopsies.
• Measurement of HIV p24, QUIN, and cytokine concentrations in cortical gray matter, cortical white matter, and deep gray matter.
• Correlation of measured concentrations with HIV gp41 immunostaining and clinical severity of HIV encephalitis.

Main Results:

• HIV gp41 immunostaining correlated with extracted HIV gag protein p24.
• Cytokine concentrations in brain tissue were generally low and did not correlate with encephalitis severity.
• Elevated TNF-alpha levels were found in deep gray matter in mild cases and in cortical areas in severe cases.
• Brain tissue and CSF QUIN concentrations were significantly increased compared to controls, but did not correlate with severity.
• Increased brain tissue levels of TNF-alpha and QUIN were observed.

Conclusions:

• Increased tissue levels of TNF-alpha and QUIN may contribute to the development of HIV-related neurologic dysfunction.
• Direct measurement of these factors in brain tissue provides insights not obtainable from CSF analysis.
• Further research is warranted to elucidate the precise mechanisms by which TNF-alpha and QUIN mediate HIV encephalitis.