Enzyme blockers slay AIDS 'giant.'

Enzyme blockers slay AIDS "giants'

Drugs that block a "sugar-trimming' enzyme important in the progression of AIDS can reduce the virus's ability to infect human blood cells and may provide a nontoxic therapy for the disease, scientists said this week. By inhibiting an enzyme called glucosidase, the drugs apparently reduce the cell-to-cell spread of the AIDS virus (HIV), as well as inhibit the formation of "giant' cells made when uninfected blood cells attach to an HIV-infected cell.

Researchers from the University of Amsterdam and The Netherlands Cancer Institute report in the Nov. 5 NATURE that the drugs castanospermine and 1-deoxynojirimycin (dNM) hinder HIV's ability to infect monocytes and lymphocytes in cell cultures by at least 100-fold. The drugs are known to block glucosidase, which trims sugars from the HIV component gp120 during virus production in host cells. A study last year at Stanford University had shown that gp120 joins with receptors on cell surfaces, leading to infection of the cell by the virus. Subsequent research indicated that at least some of the gp120 sugars influence this receptor binding.

Receptor binding by gp120 is also thought to be important in the formation of large cells that develop when uninfected cells are mixed in vitro with HIV-infected cells and their membranes fuse together. Although researchers have not detected these fragile giant cells in fresh tissues from AIDS patients, they suspect they may be important in the spread of the virus. The cells could explain, for example, how HIV--which is found in lower-than-expected numbers in AIDS patients--may maximize its effect by infecting a cluster of cells at the same time.

In the latest research, castanospermine and dNM "completely inhibited' giant-cell formation for 6 hours after the drugs were mixed with cells, and then greatly decreased it for several days after the mixing, say the scientists. The drugs, however, did not stop virus production inside already infected cells.

The latter observation is of interest because it indicates that the virus needs the proper arrangement of gp120's sugars to bind to cells, but not to replicate, says Thomas M. Folks of the Bethesda, Md.-based National Institute of Allergy and Infectious Diseases.

Folks, who does similar experiments with other enzyme-blocking agents, told SCIENCE NEWS that the low toxicity of dNM and castanospermine also is important. The Dutch researchers note that the two agents have been used in Europe to control blood glucose levels in humans.