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Morphine amplifies HIV-1 expression in chronically infected promonocytes cocultured with human brain cells
1Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404.
Abstract:
Previous studies have shown that morphine promotes the replication of human immunodeficiency virus (HIV)-1 in peripheral blood mononuclear cell cocultures. In the present study, we tested the hypothesis that morphine would amplify HIV-1 expression in the chronically infected promonocytic clone U1 when cocultured with lipopolysaccharide-stimulated human fetal brain cells. Marked upregulation of HIV-1 expression was observed in these cocultures (quantified by measurement of HIV-1 p24 antigen levels in supernatants), and treatment of brain cells with morphine resulted in a bell-shaped dose-dependent enhancement of viral expression. The mechanism of morphine's amplifying effect appears to be opioid receptor-mediated and to involve enhanced production of tumor necrosis factor-alpha by microglial cells.
Insights
Morphine amplifies human immunodeficiency virus (HIV) replication in brain cells by activating opioid receptors. This process involves increased tumor necrosis factor-alpha production by microglial cells, enhancing viral expression.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Previous research indicates morphine promotes HIV-1 replication in immune cells.
- The impact of morphine on HIV-1 expression within the central nervous system remains less understood.
Purpose of the Study:
- To investigate whether morphine amplifies HIV-1 expression in a model of infected human fetal brain cells.
- To elucidate the cellular mechanisms underlying morphine's effect on HIV-1.
Main Methods:
- Utilized a coculture system with chronically HIV-1-infected U1 cells and lipopolysaccharide-stimulated human fetal brain cells.
- Quantified HIV-1 expression by measuring p24 antigen levels in cell supernatants.
- Investigated the role of opioid receptors and tumor necrosis factor-alpha.
Main Results:
- Morphine significantly upregulated HIV-1 expression in the cocultured brain cells.
- A bell-shaped, dose-dependent enhancement of viral expression was observed with morphine treatment.
- The amplifying effect was mediated by opioid receptors and increased tumor necrosis factor-alpha production by microglial cells.
Conclusions:
- Morphine amplifies HIV-1 expression in human fetal brain cells.
- Opioid receptor signaling and microglial activation are key mechanisms in this process.
- Findings suggest potential interactions between drug use and HIV progression in the central nervous system.