Invader. in infiltrating and killing cells of the brain, JC virus (shown here in the nucleus of an oligodendrocyte) insulation bands of neurons, causing PML.
AIDS patients live longer and better than ever thanks to the improvement of drug therapy, but some bad luck still have their brains damaged by a devastating and fatal neurological disease called progressive multifocal leukoencephalopathy (PML). Now researchers have traced the path by which the virus that causes PML invades the brain cells. The results indicate that psychiatric drugs widely used can prolong the lives of AIDS patients with the disease.
Over 70% of adults harbor the JC virus, which causes PML. The virus is harmless in people with healthy immune systems, but up to 5% of patients with AIDS virus destroys brain cells called oligodendrocytes that provide myelin insulation that allows neurons to function. These patients develop tremors, partial blindness, and dementia and die in a year and a half.
To stop the JC virus to destroy brain tissue, Walter Atwood at Brown University and colleagues asked how she invaded oligodendrocytes first. They knew the work earlier than the JC virus sticks to the surface of cells and triggers the cell to engulf and swallow. They knew Thorazine, an anti-psychotic drug commonly prescribed, this process is blocked swallowing in other cell types, and that Thorazine receptors of the neurotransmitters dopamine and serotonin on the surface of the bound cell. So Atwood's team hypothesized that the JC virus on to one of these receptors as a prelude to invasion.
To test this hypothesis, the team added a number of drugs or chemicals that bind either dopamine or serotonin receptors Culture cells. Then they added virus. Only drugs which bind to serotonin receptors blocked infection. To confirm that the JC virus targets the serotonin receptors, they took cervical cancer cells grown in the laboratory who resisted infection with JC virus and designed them to produce oligodendrocytes serotonin receptor called 5-HT [2A] R. infected the modified cells JC virus, and antibodies to the 5HT [2A] receptor blocked the infection, the researchers report in the November issue 19 Science . The results mean that U.S. Food and Drug Administration approved drugs such as serotonin blocking and Thorazine cyproheptadine could prevent infection with the JC virus in the brain. A clinical trial is still in the works, but it could be soon, says Atwood.
"It's a fantastic study," said virologist cancer Kamel Khalili of Temple University in Philadelphia, Pennsylvania. A drug serotonin-blocking would not rid the body of the virus already hiding in the cells, he warns, but the results were nevertheless "great potential to help a therapeutic strategy for the PML."
Related Sites
PML Context of the National Institute of Neurological Disorders and Stroke
Walter Atwood laboratory homepage
Site Consortium for Research neurological AIDS PML
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