THE virus that causes AIDS appropriates members of a newly discovered collection of cellular proteins in order to replicate, scientists have found.
The work "suggests a new direction" in the search for AIDS drugs, said Dr. Craig Rosen, who heads the department of gene regulation at the Roche Institute of Molecular Biology in Nutley, N.J. It means molecular biologists can start to search for drugs that stymie the human immunodeficiency virus, which causes AIDS, when it tries to latch onto one of these cellular proteins, he added.
The work also illuminates basic research on how genes turn on and off. The newly discovered genes lead to the formation of proteins that are fundamental to this process. And they are "a completely new class of genes," said Dr. Stephen A. Johnston of the University of Texas Southwestern Medical Center in Dallas.
The findings are the outcome of AIDS researchers' fascination with a gene of the immunodeficiency virus known as tat. The gene has seemed an ideal target for drugs because it leads to the production of a protein, the tat protein, that seems to be unique to H.I.V. That means that if drugs could block tat, they could halt the virus, yet not affect healthy cells. In test-tube experiments, said Dr. Jeffrey Laurence, an AIDS researcher at the Cornell University School of Medicine, "if tat is blocked, you get absolutely, positively, no virus." Discovery of Gene
So much research has focused on tat, Dr. Laurence said, that "tat is the biggest file I have in my office."
Two years ago, Dr. Rosen and his colleagues, in studying the tat gene, found a gene that cells use to make a protein that binds to tat and, they thought, blocked it. Now, Dr. Rosen said, he realizes that he had just a part of the protein. With the complete molecule at hand, he found that it no longer blocked the viral gene. He said he suspected it stimulates tat, but had not yet proved that it did.
But a protein made from a similar human gene does stimulate tat, researchers report. The protein, described in the current issue of Nature, a British science journal, was discovered by Dr. Hiroshi Shibuya of Osaka University and his colleagues, and was made in the greatest amounts in T cells, white blood cells of the immune system that are devastated by H.I.V. This suggests that the virus may take hold in T cells, in part because the virus needs a protein there to replicate.
In a second paper in the current issue of Nature, Dr. Johnston and his colleagues report that yeast cells have a gene that closely resembles the human genes found by Dr. Shibuya and Dr. Rosen, indicating that the gene is an ancient one. Dr. Johnston also found that in yeast the gene is essential to cell survival and is used when the yeast cells want to turn other genes on to make proteins.
Dr. Johnston said his group had been studying its gene for about four years, but "we didn't know what to relate it to." It was not until members of his team saw Dr. Rosen's gene that they realized they were looking at something that had to do with AIDS.
Dr. Rosen said his group recently found two other human genes and two more from yeast that are similar to the genes he and the others have reported. All these genes, he said, differ slightly from each other but seem to function in the same way, by enabling the production of proteins that allow cells to begin making other proteins necessary for normal functions from gene templates. And all seem to interact with tat. Goal of Researchers
The next step, Dr. Rosen said, is to try to learn more about how the viral protein, tat, uses these cellular proteins and which, if any, it prefers. That could enable investigators to find new drugs that block tat.
So far, the work has barely begun. But the direction is clear and promising, Dr. Laurence said. "Obviously, it's the bread and butter of pharmaceutical companies and research grants," Dr. Laurence said.