Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Reuters NewMedia, Inc. - Thursday September 4 7:23 PM EDT
Gene Emery

"Although the current work is not yet ready for a clinical setting, the research boldly demonstrates that it is now possible to reverse the aim of the biochemical grappling hooks HIV-1 uses to enter cells and to employ them against the virus itself," Sanford University's Garry P. Nolan said in an editorial in the Sept. 5 issue of Cell, where the studies appear.

Acquired immune deficiency syndrome is the leading cause of death among Americans aged 24 to 44. About 750,000 Americans are currently infected, part of an epidemic that affects an estimated 30 million people worldwide.

The methods described in Cell take advantage of HIV's method of infection and turn the process against itself -- at least in the laboratory.

The AIDS virus infects disease-fighting immune cells by simultaneously latching on to two proteins -- CD4 and fusin -- protruding from the cells' surface membrane.

The virus grips CD4 and fusin with a protein of its own, known as GP120. Once attached, the virus slips inside the healthy cell and hijacks it, leaving chunks of GP120 floating on the cell's surface as a sign of its infection.

Using other virulent viruses -- in one case the rabies virus and in the other a rabies relative known as VSV -- researchers stripped them of their ability to infect normal tissues and genetically engineered the viruses to carry the CD4 and fusin proteins.

In laboratory experiments, the CD4-fusin combination attached itself to the GP120 proteins floating on the surface of the cells infected with HIV. The genetically engineered viruses can them be incorporated into the HIV-infected cell.

Normal immune cells, which do not carry the GP120 protein, are spared.

Karl-Klaus Conzelmann of the Federal Research Center for Virus Diseases of Animals in Tubingen, Germany, used the specially designed rabies virus to kill HIV-infected cells.

The second team, led by John K. Rose of the Yale University School of Medicine, went even further.

It modified VSV, or the vesicular stomatitis virus, so it could replicate itself after it entered HIV-infected immune cells known as T-cells.

When VSV killed the infected cell, it released fresh copies of the genetically engineered VSV. The new viruses were able to attack other T-cells infected with the AIDS virus. VSV, in effect, became a living drug against HIV.

"In a unique sense, the delivered 'drug' creates more copies of itself within the HIV-1 cells targeted for destruction and then moves on to seek out other HIV-1-infected cells, killing them in turn," Nolan said.

Nolan said the work could be adapted to deliver conventional drugs inside HIV-infected cells or inside cells harboring other types of disease.

But the technique raises several questions, includng whether it will be necessary or possible to design a disease-fighting virus that does not have unintended effects.

"Any use of a self-replicating 'drug' requires levels of government approval that should go to the highest levels of ethical and medical review," Nolan said.

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