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Fetal AIDS mimicked in brain-cell culture.

Fetal AIDS mimicked in brain-cell culture

Scientists have created the first successful tissue-culture model of the nervous system damage incurred by fetuses from mothers infected with the AIDS virus, or HIV. Knowledge gained from the novel system, which includes all types of fetal brain cells and permits their interaction, may eventually help researchers develop ways to treat or prevent the infection in utero, says study leader William D. Lyman, a neuropathologist at Albert Einstein College of Medicine in New York City.

Fetal nervous tissue in culture develops in a way that mimics normal human development, and once infected with HIV, it shows a pathology similar to that seen in fetuses infected in the mother's womb, Lyman reported at last week's meeting in New Orleans of the Federation of American Societies for Experimental Biology.

Lyman cultured brain tissue from 13- to 21-week-old fetuses aborted by uninfected women, and compared what he saw to his previous observations of nervous tissue from fetuses aborted by HIV-infected women. The latter work was presented last June at the International Conference on AIDS in Stockholm. HIV genetic material was found in those tissues.

Although other scientists have developed cell-culture systems to study HIV infection of the nervous system, none has used organized human brain tissue of more than one cell type to represent normal nervous system development. And no previous research could reproduce signs of severe AIDS infection in tissue culture, says neurologist Richard W. Price at Memorial Sloan-Kettering Cancer Center in New York City.

Scientists have found HIV in white blood cells in the brain and have suspected that brain cells can be infected, but Price says previous studies have not convincingly revealed whether HIV directly targets the major cell types in the brain -- neurons, astrocytes and oligodendrocytes. Lyman's studies indicate that in the fetal brain HIV may directly infect and injure brain cells. He reports that infected tissue cultures showed cell death and disruption of the normal nervous tissue arrangement similar to what occurs in utero and reminiscent of some aspects of the neuropathology seen in cases of pediatric AIDS. In addition, Lyman found that the tissue-culture cells accumulated excess fluid, a sign of inflammation.

The clinical symptoms of pediatric AIDS also suggest to Lyman that HIV directly damages the nervous system. "The vast majority of children born with congenital HIV infection exhibit retarded neurological development," Lyman says. They speak late, walk late and always perform among the lowest 2 percent for their age in tests of cognitive skills, he notes.

In addition, many children who develop AIDS-related neurological disease suffer from a deformity of facial features, called AIDS embryopathy, that "is suggestive of a pathologic event occurring very early on in pregnancy that affects cells that go into making up, amongst other things, the nervous system," Lyman says. He notes that the defects are similar to other facial deformities originating early in a pregnancy.

If brain cells are infected, it is important to know which cell types might harbor the virus, says neuropathologist Leroy R. Sharer of the University of Medicine and Dentistry of New Jersey in Newark. Lyman and his team are now using the cell-culture system to address that question and to determine how the infection varies as a function of fetal age, time of infection, amount of virus and pathway of infection. They are also looking at which HIV types are the most pathogenic.

The severity of pediatric AIDS, Lyman says, probably depends on when the fetus is exposed to the virus, the amount and type of HIV and the genetic makeup of the fetus itself. Lyman hopes that what he learns from his in vitro system will ameliorate the effects of pediatric AIDS, which by 1991 will have struck approximately 10,000 children in the United States, he says. His system also could be used to explore how a given drug or treatment taken during pregnancy affects the fetal nervous system, he adds.
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Author:Wickelgren, Ingrid
Publication:Science News
Date:Apr 1, 1989
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