'Competition' cause of AIDS dementia?

"Competition' cause of AIDS dementia?

Structural similarities between AIDS-causing viruses and a protein that stimulates nerve cells may contribute to the dementia common in AIDS patients, and thus may provide a way to reverse that dementia, scientists said last week. The researchers suggest that the similarities create a competition between virus and protein for binding sites on neurons-- leading to inhibition of nerve function by the viruses, and in turn causing symptoms associated with dementia.

Since the AIDS-causing HIV-1 virus was first isolated from brain tissue in 1985, there have been multiple reports of the virus found in the nervous system of AIDS patients. Over the same period of time, clinicians began routinely observing AIDS patients for signs of dementia, including memory impairment, apathy and poor concentration. Now recognized in at least two-thirds of AIDS patients, signs of dementia recently were added to a revised definition of the deadly disease (SN: 8/29/87, p.136). But the actual cause of AIDS dementia has been unknown, despite the fact that the amount of HIV-1 in the spinal fluid is related to the severity of dementia.

"Even though there is this dementia in AIDS, it is clear that HIV-1 does not infect the neurons themselves,' Mark E. Gurney of the University of Chicago told SCIENCE NEWS. Gurney, co-worker Mark R. Lee and David D. Ho of the Cedars-Sinai Medical Center in Los Angeles studied the interaction between HIV-1 and factors that are known to control neuronal growth and function. What they found, says Gurney, could help explain what is causing AIDS-related dementia.

"[The HIV-1 virus] infects the monocyte cells in the brain,' says Gurney. "So how does an infected monocyte, which isn't a nerve cell, cause dementia? There must be an indirect mechanism.' That mechanism, Gurney and his coauthors report in the Aug. 28 SCIENCE, may be the competition between the virus and a protein called neuroleukin.

First described by Gurney and others in 1986, neuroleukin is secreted by lymphocyte cells, stimulates antibody production by other blood cells and influences the growth of neurons in embryos. In the recent study, the scientists found that a segment of neuroleukin is very similar in structure to the HIV-1 component called gp 120. Experiments using 10-day-old chick embryos showed that the addition of either whole HIV-1 or gp 120 suppressed the activity of neuroleukin.

According to Gurney, the cause of the dementia in AIDS apparently differs from that of other dementias: "In Alzheimer's, you have actual death of nerve cells, and you don't in AIDS. . . . It's as if the [AIDS-related] dementia is a by-product, and the brain is an innocent bystander.' The absence of cell death directly due to viruses may mean that the dementia could be reversed, he says.

This premise is supported by results from a recently reported study, in which a small number of AIDS patients treated with the drug zidovudine (formerly known as AZT) showed improvement of dementia. That success, suggests Gurney, may have been due to reduce competition: "If you control the infection, you reduce the gp 120 and the neuroleukin can start acting again.'

But Gurney says there are many questions without answers. The current results come from experiments in embryonic, rather than adult, nerve tissue. Neuroleukin's exact role in the adult brain remains unclear. That discrepancy, he says, creates a "weak part in generalizing our results to dementia in adult AIDS patients.' He and his co-workers are planning to inject gp 120 into the brains of adult laboratory animals, and watch for signs of dementia. Another question the researchers say must be answered is whether gp 120 also interferes with the immune-system functions of neuroleukin.